Library · Biology & lab methods

What Lipid & Membrane Engineering got wrong, from 62 theses

Summary written by a model from the records below: The records evaluate engineering methodologies for lipid nanoparticles, liposomes, reconstituted membrane models, and detergent solubilization strategies. Across these applications, researchers encountered frequent setbacks including carrier aggregation, poor intracellular transfection, protein destabilization during extraction, and underperformance relative to simpler non-lipid baselines. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.

62
theses
20
institutions
73
failure records
6
failure modes

Plus 10 problems the authors left open, listed at the end.

Failure modes, by theses reporting them

Select a mode to jump to its records.

Detergent and polymer extraction causes membrane protein destabilization, denaturation, and contamination
15
15 theses · 9 institutions · 16 records
Lipid nanoparticles and vesicles suffer from colloidal instability, aggregation, and precipitation
15
15 theses · 6 institutions · 15 records
Suboptimal lipid compositions and charge ratios impair cargo encapsulation, release, and transfection
16
16 theses · 9 institutions · 17 records
Lipid-based formulations are outperformed by unencapsulated payloads and non-lipid delivery methods
10
10 theses · 9 institutions · 11 records
Surface functionalization and targeting ligand conjugation fail to achieve intended delivery profiles
5
5 theses · 4 institutions · 7 records
Supported bilayers and planar membrane models suffer from substrate artifacts, defects, and mechanical fragility
7
7 theses · 6 institutions · 7 records

Detergent and polymer extraction causes membrane protein destabilization, denaturation, and contamination

15 theses · 9 institutions

Solubilizing membrane proteins with non-ionic detergents or amphiphilic polymers frequently triggers protein unfolding, irreversible aggregation, and disruption of native protein interactions. In addition, these extraction agents introduce background noise in structural imaging and lead to the co-purification of unwanted host contaminants.

Considered and rejected

Considered and rejected: Rejected detergent biochemical purification and nanodisc reconstitution of GPCRs due to delipidation, conformation loss, endogenous protein contamination, and lack of orientation control.

VIRION DISPLAY UNCOVERS MD-1 AS THE ENDOGENOUS AGONIST FOR THE ORPHAN RECEPTOR GPRC5B · Johns Hopkins · PhD

Considered and rejected

Considered and rejected: Rejected full-length GPCR reconstitution into bilayers because the required detergents interact with lipid bilayers and alter membrane physical properties.

MOLECULAR MECHANISMS OF THE FORMATION OF ENDOCYTIC PATCHES AND THE INITIATION OF ACTIN POLYMERIZATION IN FAST ENDOPHILIN MEDIATED ENDOCYTOSIS · Penn · PhD

Tried and failed

Detergent solubilisation for membrane protein cryo-EM applied to large bacterial membrane protein complexes. Reason: Large detergent micelle shells occluded structural features and produced substantial cryo-EM background noise

Investigating the protein subcomplexes from a conjugative Type IV Secretion System · Imperial · Doctorate

Tried and failed

nanodisc polymer membrane extraction applied to bacterial outer membrane lipoproteins. Reason: Signal peptidase cleavage yielded soluble truncated proteoforms instead of nanodisc-bound lipidated protein

Investigations of New Delhi metallo-β-lactamase : the roles of lipid modification, allosteric inhibition, and MBL-superfamily enzymes in the development of biologics · UT Austin · PhD

Tried and failed

detergent or polymer solubilisation for particle purification applied to membrane-embedded protein pore complexes. Reason: failed to yield homogeneous pore particles during extraction from liposomes

Function and mechanism of the gasdermin family · Harvard · PhD

Tried and failed

non-ionic detergent solubilization and affinity purification applied to integral membrane glycosyltransferases. Reason: detergent co-purified abundant non-specific endogenous host membrane protein contaminants

Biochemical Characterization of Glycan Assembly Pathway Enzymes · MIT · PhD

Tried and failed

non-ionic detergent lysis for single-molecule pulldown applied to membrane-associated protein complexes. Outcome: no signal. Reason: detergent solubilization disrupted native membrane protein interactions, preventing complex detection

Untangling Par complex dynamics during embryogenesis using single-molecule TIRF microscopy · UT Austin

Tried and failed

mild non-ionic detergent solubilisation for co-fractionation mass spectrometry applied to membrane-associated protein complexes. Outcome: no signal. Reason: mild non-ionic detergents failed to extract and systematically depleted structural cytoskeletal actin proteins

The protein organization of a red blood cell · UT Austin · PhD

Tried and failed

styrene-maleic acid copolymer solubilization into nanodiscs applied to large monotopic membrane proteins. Reason: polymer failed to extract and solubilize the membrane proteins from lipid membranes

Biochemical Characterization of Glycan Assembly Pathway Enzymes · MIT · PhD

Tried and failed

membrane protein solubilization with harsh non-ionic detergents applied to transmembrane palmitoyltransferase enzyme complexes. Outcome: unstable. Reason: detergents Triton X-100, C9G, and LDAO induced complete protein aggregation

STRUCTURAL AND FUNCTIONAL STUDIES OF THE DHHC9 SUBFAMILY OF PROTEIN ACYLTRANSFERASES · Cornell · PhD

Tried and failed

nanodisc incorporation for solution NMR applied to membrane pore protein complexes. Reason: insufficient yield and poor sample homogeneity prevented 3D solution NMR structural studies

Biophysical studies of biological nanopores used for biopolymer sequencing · Imperial · PhD

Tried and failed

multiple pendant detergents and amphipols for solubilisation applied to membrane transport protein extraction. Outcome: unstable. Reason: failed to efficiently extract and stabilize the protein, causing aggregation during size-exclusion chromatography

Structural and functional characterisation of the human vitamin c transporters · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected SMA/DIBMA lipid nanodiscs in favor of traditional DDM detergent because polymer nanodiscs previously had undesirable reagent interactions disrupting downstream assays.

Regulation of ABCG2 through interactions with Alpha-1-Acid Glycoprotein and EMMPRIN · Nottingham · Master's

Considered and rejected

Considered and rejected: Standard alcoholic fixation and detergent permeabilization rejected for phosphoinositide microscopy because detergents disrupt membranes and extract PIs.

A lipidomic approach to elucidating the effects of antifungal compounds on signalling in fungi · Imperial · Doctorate

Considered and rejected

Considered and rejected: Rejected RIPA and Triton X-100 detergent lysis for organelle interactome pulldowns because detergents disrupt membrane integrity, labile protein interactions, and endosomal vesicles.

Activity-dependent activation of mTORC1 in neurons · Johns Hopkins · PhD

Considered and rejected

Considered and rejected: Purifying solubilized GPCRs directly in detergent micelles away from membranes, due to protein unfolding, conformational instability, and MS incompatibility.

Elucidating the Role of Two Inotropic Agents in Cardiac Hypertrophy: the Ceramides and Apelins · University of Washington · PhD

Lipid nanoparticles and vesicles suffer from colloidal instability, aggregation, and precipitation

15 theses · 6 institutions

Formulations lacking adequate steric stabilizers, lyoprotectants, or suitable lipid-to-particle ratios rapidly precipitate, aggregate, or exceed critical size thresholds during assembly and storage. High membrane curvature, adverse surface charge modifications, and thermal destabilization similarly compromise particle integrity and shelf life.

Tried and failed

incorporating cationic lipids in microfluidic lipid formulations applied to mRNA lipid nanoparticles. Outcome: unstable. Reason: formulations failed monodispersity and size quality control criteria and precipitated out of solution

Design and Formulation Optimization of Lipid Nanoparticles Carrying MRNA to the Heart and the Pancreas · Georgia Tech · PhD

Tried and failed

cationic lipid-mRNA complexes on mesoporous scaffolds applied to sustained in vivo mRNA delivery. Outcome: unstable. Reason: lipoplexes degraded rapidly at physiological temperature losing transfection capacity within days

Mesoporous Silica Rods Scaffolds for the generation of adaptive immune responses · Harvard · PhD

Tried and failed

formulation without steric stabilizer lipid applied to lipid nanoparticles. Outcome: unstable. Reason: aggregation and instability leading to particle diameter exceeding size quality control threshold (>200 nm)

UTILIZING HIGH-THROUGHPUT IN VIVO NANOPARTICLE SCREENS TO IMPROVE DRUG DELIVERY · Georgia Tech · PhD

Tried and failed

supported lipid bilayer coating applied to mesoporous silica microparticles. Outcome: unstable. Reason: low lipid-to-particle ratio caused particle aggregation

Materials to enable and enhance T-cell immunotherapies · Harvard · PhD

Tried and failed

nanoprecipitation with lipid-peg surfactant applied to hydrophobic conjugated polymers. Outcome: unstable. Reason: produced colloidally unstable nanoparticles with non-specific emission quenching

Modulating the properties of conjugated systems towards bioelectronics and bio-imaging · Imperial · PhD

Tried and failed

thin-film freeze-drying without lyoprotectant applied to lipid nanoparticle powder reconstitution. Outcome: unstable. Reason: absence of lyoprotectant caused vesicle damage and particle aggregation during freezing and drying

Lipid-based nanoparticles for drug delivery · UT Austin · Doctorate

Tried and failed

cell membrane-coated nanoparticles without hydrophilic shielding polymer applied to intravenous nanoparticle delivery. Outcome: unstable. Reason: lack of protective surface coating caused particle aggregation and systemic toxicity in circulation

An apoptotic body-inspired nanoparticle to modulate inflammatory macrophages · UT Austin · PhD

Lost to a baseline

C16 alkyl chain ionizable lipids in the initial RNP LNP library resulted in particle aggregation (>1 µm size) and poor Cas9 protein encapsulation compared to C12 and C14 lipids.

LIPID NANOPARTICLES ALLOW INTRACELLULAR PROTEIN DELIVERY FOR MODULATION OF DIFFICULT THERAPEUTIC TARGETS · Penn · PhD

Considered and rejected

Considered and rejected: Pivoted away from synthesizing ~1 um liposomes due to severe batch-to-batch size variability, opting for PLGA microparticles and targeted LNPs/hydrogels instead

Targeting the draining lymphatic network as a regulator of melanoma growth · Georgia Tech · PhD

Considered and rejected

Considered and rejected: Rejected DSPC, DOPE, and DOTAP formulations (100% lipid or with cholesterol/DSPE-PEG) for direct lipid coating of RENPs because they resulted in aggregation

Rare-Earth Nanoparticles for Non-invasive In Vivo Imaging of Immune Cells in Cancer Immunotherapy · MIT · PhD

Tried and failed

photoswitchable lipid bilayer formulation without membrane stabilizer applied to liposomal cargo retention at physiological temperature. Outcome: unstable. Reason: lack of cholesterol led to membrane destabilization and cargo leakage upon thermal incubation

LisNRs : a novel class of liposomal contrast agents for molecular MRI · MIT · PhD

Tried and failed

hydrophilic coating of polymer microfluidic channels applied to solvent-based liposome synthesis devices. Outcome: unstable. Reason: coatings suffered wash-out instability, causing channel wetting and lipid precipitation blockage

Developing artificial cells for delivering drug molecules to micro-engineered heart tissue · Imperial · PhD

Tried and failed

post-insertion of lipid-peg micelles applied to cholesterol-anchored aptamer liposomes. Outcome: unstable. Reason: micelle insertion displaced single-cholesterol anchored conjugates out of the bilayer into solution

Analysis of the properties of phospholipid bilayers for drug delivery using solid-state NMR · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected evaluating liposomes below 100 nm diameter due to significantly decreased stability from elevated membrane surface energy/curvature.

Biomimetic water-based lubrication: an exploration into vesicle lubrication · Imperial · Doctorate

Tried and failed

monovalent charged lipid electrostatic stabilization applied to colloidal lipid nanodiscs. Outcome: unstable. Reason: electrostatic repulsion insufficient to maintain disc structure under physiological ionic strength conditions

Layer-by-Layer Nanoparticles for Cytokine Delivery · MIT · PhD

Suboptimal lipid compositions and charge ratios impair cargo encapsulation, release, and transfection

16 theses · 9 institutions

Unfavorable helper lipid choices, permanently charged cationic lipids, and improper lipid-to-cargo or charge ratios hinder payload encapsulation and release kinetics. These compositional deficiencies frequently result in poor intracellular delivery, low in vivo transfection efficiency, and elevated cytotoxicity.

Tried and failed

nanoparticle formulation at low lipid to cargo ratio applied to lipid nanoparticles encapsulating nucleic acids. Outcome: worse than baseline. Reason: insufficient lipid mass ratio resulted in poor cargo encapsulation efficiency

Development of Lipid Nanoparticles for RNA Delivery to Hematopoietic Stem Cells and Development of Alternative Model Systems for Nanoparticle Discovery · Georgia Tech · PhD

Tried and failed

permanently charged cationic lipid substitution in nanoparticles applied to RNA delivery formulations. Outcome: worse than baseline. Reason: produced significantly lower transfection expression compared to degradable ionizable lipid benchmarks

Development of Chemically-Defined Platform Materials for Localized Delivery of RNA Therapeutics · MIT · PhD

Tried and failed

lowering cationic lipid to RNA ratio applied to lipid nanoparticle nucleic acid delivery. Outcome: worse than baseline. Reason: lowest N/P ratio nanoparticles unexpectedly showed higher cytotoxicity than intermediate ratios

Lipid-based nanoparticles for drug delivery · UT Austin · Doctorate

Tried and failed

neutral or anionic lipid nanoparticle formulation applied to systemic mRNA delivery to lungs. Outcome: no signal. Reason: neutral and anionic helper lipids failed to facilitate measurable pulmonary biodistribution or transfection

Next-Generation Lipid Nanoparticle Formulations for Non-Liver Delivery of Nucleic Acid-Based Therapies and Vaccines · Georgia Tech · PhD

Tried and failed

co-encapsulating disaccharide cryoprotectant during lipid nanoparticle assembly applied to polymer-coated lipid nanoparticle RNA delivery. Outcome: worse than baseline. Reason: sucrose co-encapsulation reduced transfection efficiency despite maintaining acceptable size and polydispersity

Novel virus-mimicking polymer-functionalised lipid nanoparticles for enhanced intracellular RNA delivery and stable storage at ambient temperatures · Imperial · PhD

Tried and failed

intermediate charge ratio complexation in lipid nanoparticles applied to siRNA delivery and gene silencing. Outcome: worse than baseline. Reason: intermediate charge ratios exhibited slowest release kinetics, reducing downregulation efficacy

Lipid-based nanoparticles for drug delivery · UT Austin · Doctorate

Lost to a baseline

DSPC helper lipid formulation was outperformed up to four-fold in vivo by DOPE-containing LNPs for mRNA delivery

Engineering Lipid Nanoparticle-Mediated Delivery of Nucleic Acids to Lymphoid Organs and Immune Cells · UT Southwestern

Lost to a baseline

In vivo delivery of Cas13-nLuc mRNA via MC3, Lipid 5, and LP01 LNPs resulted in lower liver luminescent flux compared to cKK-E12 LNPs.

Development of an mRNA-based prophylactic for protection against nerve agent toxicity · Georgia Tech · PhD

Considered and rejected

Considered and rejected: Rejected rehydration of dried lipid films in the presence of mRNA and extrusion due to complete loss/degradation of mRNA during sonication and extrusion.

Mesoporous Silica Rods Scaffolds for the generation of adaptive immune responses · Harvard · PhD

Tried and failed

in vitro screening to predict in vivo delivery applied to lipid nanoparticle nucleic acid formulations. Outcome: did not generalise. Reason: In vitro delivery efficacy showed no correlation with in vivo delivery across hundreds of formulation variants

UTILIZING HIGH-THROUGHPUT IN VIVO NANOPARTICLE SCREENS TO IMPROVE DRUG DELIVERY · Georgia Tech · PhD

Tried and failed

ternary uncharged lipid mixtures applied to intracellular chemotherapeutic drug delivery. Outcome: worse than baseline. Reason: insufficient interaction with cell surfaces due to lack of charged head groups

Engineering liposomal particles for direct, intracellular delivery of therapeutic molecules · UT Austin · PhD

Tried and failed

lysolipid temperature-sensitive liposome formulation applied to thermally triggered vesicle payload release. Outcome: no signal. Reason: minimal cargo release occurred at target phase transition temperature despite formulation adjustments

Development of stimuli-responsive vesicles as distributed artificial organelles · Imperial · PhD

Tried and failed

lipid nanocapsule drug delivery formulation applied to in vivo parasitic worm infection. Outcome: no signal. Reason: lack of drug release and cellular internalization in vivo

Advancing first principle-based molecular dynamics of biological systems with machine learning · EPFL · PhD

Considered and rejected

Considered and rejected: Rejected microfluidic Tesla mixers and flash nanoprecipitation because Tesla mixers function primarily for lipid-polymeric hybrids and flash nanoprecipitation resulted in lower encapsulation efficiency.

Nanoparticle Fabrication via Microfluidics as a Therapeutic for Influenza A Virus · University at Buffalo · PhD

Considered and rejected

Considered and rejected: Rejected C3 LNP formulation at 20:1 N:P ratio despite higher in vitro delivery due to enhanced cytotoxicity and excess free ionizable lipid.

IONIZABLE LIPID NANOPARTICLES FOR IN UTERO GENE EDITING OF CONGENITAL DISEASE · Penn · PhD

Tried and failed

binary lipid carrier solid dispersion applied to poorly water-soluble triterpenoid bioavailability enhancement. Outcome: no signal. Reason: binary matrix failed to enhance solubility and gave extremely low yield without an additional surfactant

Phase 1 clinical trial evaluating safety, bioavailability, and gut microbiome with a combination of curcumin and ursolic acid in lipid enhanced capsules · UT Austin · PhD

Tried and failed

incorporating cationic cholesterol in lipid nanoparticles applied to intratumoral mRNA delivery. Outcome: worse than baseline. Reason: negatively enriched compared to neutral cholesterol formulations during in vivo screening

Translational Design of Lipid Nanoparticles (LNPs) to Deliver mRNA Therapies to Solid Tumors and to the Lungs · Georgia Tech · PhD

Lipid-based formulations are outperformed by unencapsulated payloads and non-lipid delivery methods

10 theses · 9 institutions

Encapsulating therapeutic agents in liposomes or lipid nanoparticles often yields lower cellular delivery, drug penetration, or transfection efficiency than free drug solutions, electroporation, or peptide vectors. Certain lipid vehicle designs also exhibit higher cytotoxicity and inferior cargo loading compared to alternative polymeric or surfactant platforms.

Lost to a baseline

Cationic lipid library (e.g., X10-C12) and PEG-mediated RNP delivery achieved parity but failed to surpass control methods (TransIT-2020 and dried protein) in preliminary biolistic Cas9 RNP editing

Improving biolistic delivery for DNA and protein systems in plants · Iowa State · PhD

Lost to a baseline

Encapsulated rutin in lipid nanoparticles (LNPs) showed lower penetration (ART 16.3–16.5 MGV/px) than unencapsulated solutions in lemongrass oil (33.1 MGV/px) or MCT (29.1 MGV/px) in finite-dose assays

smartOX - Smarte Antioxidantien zur Pflege und Regeneration sensitiver Haut smartOX - Smart antioxidants for the care and regeneration of sensitive skin · University of Marburg · PhD

Lost to a baseline

Peptide-only nanoparticles assembled manually or via Spark enabled higher DNA expression than all hybrid lipid-peptide formulations.

Use Of Microfluidic Systems For Assembly Of Nucleic Acid Nanoparticles · Johns Hopkins · Master's

Lost to a baseline

At 100 µM doxorubicin, binary liposomes containing 3 mol% DOTAP killed only 8 ± 1% of cells compared to ~70% killed by free doxorubicin

Engineering liposomal particles for direct, intracellular delivery of therapeutic molecules · UT Austin · PhD

Lost to a baseline

Cross-linked liposome retention after 10 days (1.6% to 2.9%) was inferior to non-crosslinked standard liposomes (21.5% to 34.9%).

Pt(IV) anticancer prodrugs and liposomal encapsulation · Oxford · PhD

Lost to a baseline

Lipid nanoparticles (LNPs) achieved only 20.56% transfection efficiency in PCFs compared to 52.24% with electroporation.

Etablierung eines optogenetischen Systems zur lichtinduzierten Proteinbiosynthese in humane Stammzellen für therapeutische Anwendungen · Leibniz Universität Hannover · PhD

Lost to a baseline

At 100 µM doxorubicin, unencapsulated (free) doxorubicin killed ~70% of cells, whereas ternary liposomes lacking DOTAP killed only 25% of cells.

Engineering liposomal particles for direct, intracellular delivery of therapeutic molecules · UT Austin · PhD

Lost to a baseline

In small 200 µm diameter spheroids, antibody alone achieved lower outgrowth than liposome combination.

STUDIES ON PHASE-TRANSITIONING LIPID BILAYERS: FROM INTEGRAL CARRIERS FOR RADIONUCLIDE THERAPIES TO MODEL MEMBRANES FOR STUDYING THE ACTION OF DAPTOMYCIN · Johns Hopkins · PhD

Tried and failed

PEGylated lipid stabilization for protein encapsulation applied to lyotropic liquid crystalline nanoparticles. Outcome: worse than baseline. Reason: loaded significantly less protein cargo than poloxamer stabilization despite having larger internal water channels

Advanced single particle characterisation of cargo loading in therapeutic particles · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected off-the-shelf cationic lipid formulations (e.g., DSTAP) or PEI for microbubble cargo loading due to unstable loading/enzymatic degradation and high polymer toxicity.

Microbubble-Assisted Ultrasound Guided Immunotherapy of Cancer: A Novel Microbubble Platform for Cancer Immunotherapy · UT Southwestern · PhD

Considered and rejected

Considered and rejected: Rejected lipid/liposome-based transfection (e.g., FuGENE, Lipofectamine) for delivering CRISPR components into HUVECs due to high cytotoxicity, cytoplasmic nucleic acid degradation, and low efficiency compared to electroporation.

Dynamics of cytokine induced E-selectin expression in endothelial cells · Nottingham · PhD

Surface functionalization and targeting ligand conjugation fail to achieve intended delivery profiles

5 theses · 4 institutions

Functionalizing lipid nanoparticles or liposomes with small fragments, metal chelators, or PEG chains often fails to improve target cell binding, in vivo biodistribution, or enzymatic responsiveness. Incomplete conjugation density, unintended rapid clearance to the liver, and activity loss during reconstitution further compromise targeted lipid formulations.

Tried and failed

scFv targeting moieties instead of full antibodies applied to targeted lipid nanoparticle delivery. Outcome: worse than baseline. Reason: scFv conjugated nanoparticles failed to outperform full monoclonal antibody conjugates in delivery potency

Antibody-Conjugated Lipid Nanoparticles Could Enable Targeted Delivery to Long-Term Hematopoietic Stem Cells to Treat Blood Diseases · Harvard · Master's

Tried and failed

lyophilization and reconstitution of functionalized liposomal formulations applied to therapeutic immunomodulatory protein-lipid nanoparticles. Outcome: worse than baseline. Reason: freeze-drying and reconstitution reduced target tumor cell lysis activity compared to freshly prepared formulations

Multivalent immunomodulators for CAR T cell manufacturing and T cell-engager immunotherapy · Georgia Tech · PhD

Tried and failed

direct liposome encapsulation of proteins applied to protein delivery vehicle preparation. Reason: low phase transition temperature caused cargo leakage, while higher transition temperature lipids caused thermal artifacts

Development of tools and methods for protein identification: From single molecules to in vivo applications · EPFL · PhD

Tried and failed

cationic lipid nanoparticle delivery applied to circulating blood cell targeting in vivo. Outcome: no signal. Reason: nanoparticles delivered cargo to liver and marrow but lacked statistically significant delivery to circulating blood cells

Development of Lipid Nanoparticles for RNA Delivery to Hematopoietic Stem Cells and Development of Alternative Model Systems for Nanoparticle Discovery · Georgia Tech · PhD

Considered and rejected

Considered and rejected: Rejected 1X antibody input mass during maleimide lipid conjugation because it failed to achieve targeted antibody densities per liposome

Multivalent immunomodulators for CAR T cell manufacturing and T cell-engager immunotherapy · Georgia Tech · PhD

Considered and rejected

Considered and rejected: LNPs formulated with proprietary ionizable lipids IL4-IL7 (LNP-017 through LNP-020) designed for extended circulation without antibody conjugation were rejected due to poor HSC targeting and preferential liver accumulation

Antibody-Conjugated Lipid Nanoparticles Could Enable Targeted Delivery to Long-Term Hematopoietic Stem Cells to Treat Blood Diseases · Harvard · Master's

Considered and rejected

Considered and rejected: Rejected PEGylation of liposomes because attached polyethylene glycol chains impede outer shell hydration lubrication.

Biomimetic water-based lubrication: an exploration into vesicle lubrication · Imperial · Doctorate

Supported bilayers and planar membrane models suffer from substrate artifacts, defects, and mechanical fragility

7 theses · 6 institutions

Planar lipid bilayers and tethered membranes frequently develop electrical leakage defects, delaminate during physical patterning, or alter lipid mobility due to underlying solid supports. Planar configurations also fail to replicate natural membrane curvature, leading to molecular simulation boundary artifacts and membrane runoff.

Tried and failed

mechanical scratch patterning of thin surface coatings applied to supported lipid bilayer on conductive polymer. Outcome: unstable. Reason: scratching unintentionally delaminated the underlying soft polymer film along with the lipid bilayer

THE DEVELOPMENT OF COMPLEX BIOMEMBRANE PLATFORMS TO INVESTIGATE THE IMPACT OF MEMBRANE DISRUPTING AGENTS ON MEMBRANE BIOPHYSICAL PROPERTIES · Cornell · PhD

Lost to a baseline

Electrical sealing properties of NHC-based tBLMs (transmembrane resistance 177-194 kΩ/cm²) were inferior to the reference thiol anchor lipid DPhyTL (2.48-3 MΩ/cm²) due to membrane defect density

Moving in the right direction: Functionalized N-heterocyclic carbenes to assemble surface-bound biomolecular architectures for applications from biosensing to synthetic lipids · TU Wien · PhD

Considered and rejected

Considered and rejected: Rejected single-lased (1X-LIG) hydrophilic substrates for sensing because of water layer accumulation, membrane runoff over the stem, and large EMF drift.

Development and characterization of ion-selective electrodes based on laser-induced graphene for food safety and precision agriculture · Iowa State · PhD

Considered and rejected

Considered and rejected: Supported lipid bilayers and planar monolayers were avoided as primary models due to absence of bilayer curvature, substrate effects on lipid mobility, and vulnerability to air oxidation.

Second harmonic scattering of water in a biological context · EPFL · PhD

Considered and rejected

Considered and rejected: Rejected planar freestanding lipid bilayers as realistic cell membrane models because they are fragile, lack curvature, and naturally tend to close into vesicles to avoid exposed hydrophobic edges.

Molecular ordering effects in bulk and at lipid/water nanoscopic interfaces: A story of water, light, and order · EPFL · PhD

Tried and failed

molecular dynamics of finite planar lipid bilayer applied to protein-membrane binding affinity simulation. Reason: Proteins preferentially adhered to hydrophobic periodic boundary or edge artifacts rather than the planar bilayer surface.

Characterizing & modelling the bio-nano interface · Imperial · PhD

Tried and failed

neutron spin echo on lipid bicelles applied to membrane protein dynamics. Outcome: no signal. Reason: the bicelle matrix was too fluidic, causing translational diffusion to dominate the internal dynamics signal

Biochemical and Biophysical Characterization of Archaeal Intramembrane Aspartyl Proteases – Decoding Substrate Specificity, Kinetic Properties, and Solution Structure · Georgia Tech · PhD

Left open by the authors

Problems the authors named and did not get to.

Left open

Synthesize and formulate ionisable polymer-functionalised lipid nanoparticles for RNA delivery. Blocker: Requires a wet-lab environment and chemical/biological materials for nanoparticle synthesis and extrusion

Novel virus-mimicking polymer-functionalised lipid nanoparticles for enhanced intracellular RNA delivery and stable storage at ambient temperatures · Imperial · PhD

Left open

Develop lipid nanoparticle-based mRNA delivery strategies for Cas9-retron genome editing systems. Blocker: Requires a wet lab for lipid nanoparticle formulation, mRNA synthesis, and in vitro/in vivo delivery assays

Discovery of novel systems for genome editing · UT Austin · PhD

Left open

Incorporate mRNAs containing modified UTRs into lipid nanoparticles to decrease off-target liver expression. Blocker: Requires wet-lab synthesis of modified mRNAs, formulation of lipid nanoparticles, and in vivo/in vitro delivery assays.

Development of Lipid Nanoparticles for RNA Delivery to Hematopoietic Stem Cells and Development of Alternative Model Systems for Nanoparticle Discovery · Georgia Tech · PhD

Left open

Modify the surface of polymer-functionalised lipid nanoparticles with specific targeting ligands for targeted RNA delivery. Blocker: Requires wet lab facilities for chemical synthesis, lipid nanoparticle formulation, and targeting assays

Novel virus-mimicking polymer-functionalised lipid nanoparticles for enhanced intracellular RNA delivery and stable storage at ambient temperatures · Imperial · PhD

Left open

Evaluate how RNA design and LNP formulations impact antigen and inflammatory kinetics in mRNA vaccines. Blocker: Requires a wet lab to formulate lipid nanoparticles (LNPs), design RNA sequences, and measure in vivo or in vitro kinetics.

Engineering kinetics of immunotherapies and vaccines · MIT · PhD

Left open

Test therapeutically relevant nucleic acid payloads formulated in lipid nanoparticles in an in vivo atherosclerosis mouse model. Blocker: Requires wet lab facilities, microfluidic LNP formulation, and in vivo animal disease models

Design and Formulation Optimization of Lipid Nanoparticles Carrying MRNA to the Heart and the Pancreas · Georgia Tech · PhD

Left open

Deliver therapeutic mRNA including CRISPR/Cas9 to the brain using lipid nanoparticles. Blocker: Requires a wet lab, chemical synthesis, microfluidic equipment, and in vivo animal models for brain delivery.

Development of Chemically-Defined Platform Materials for Localized Delivery of RNA Therapeutics · MIT · PhD

Left open

Deliver base and prime editors encapsulated in lipid nanoparticles to the lung endothelium in vivo. Blocker: Requires wet lab facilities for LNP formulation and animal models for in vivo delivery assays

Development and applications of peptide barcoded nanoparticles for high-throughput screening of mRNA delivery materials in vivo · MIT · PhD

Left open

Evaluate mRNA delivery by barcoded lipid nanoparticles to intratumoral immune cell subtypes in immunocompetent mice with spontaneous tumors. Blocker: Requires wet lab facilities, barcoded LNP formulations, and in vivo animal tumor models

Translational Design of Lipid Nanoparticles (LNPs) to Deliver mRNA Therapies to Solid Tumors and to the Lungs · Georgia Tech · PhD

Left open

Formulate top five ubiquibody constructs as mRNA in lipid nanoparticles and evaluate beta-catenin degradation in vitro and in mouse models. Blocker: Requires wet lab facilities, LNP formulation equipment, and animal model testing facilities

SCREENING THE E3 LIGASE LANDSCAPE FOR RATIONAL DESIGN IN UBIQUIBODY-MEDIATED TARGETED PROTEIN DEGRADATION · Cornell · PhD

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