Metastability in lipid based particles exhibits temporally deterministic and controllable behavior

Jacoby, Guy; Cohen, Keren; Barkan, Kobi; Talmon, Yeshayahu; Peer, Dan; Beck, Roy

doi:10.1038/srep09481

Cited by 16 publications

(18 citation statements)

References 30 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that it is possible to kinetically trap super-swelled states that remain stable and with maximum ordering. These results are in line with the general observation that metastability in lipid systems allows for additional control and diversity of the phase space (32).…”

Section: Significancesupporting

confidence: 90%

Super-swelled lyotropic single crystals

Kim

Song

Leal

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lipids self-assemble into diverse supramolecular structures that exhibit thermotropic and/or lyotropic behavior. Lyotropic mesophases, where membranes conform to periodic minimal surfaces dividing two nonpenetrating aqueous subspaces, are arguably one of the most intriguing phases of lipid materials. Traditional 3D bicontinuous cubic lipid materials appear as a polycrystal of varying degrees of order. When exposed to water, the properties of the molecular building blocks of the membrane determine specific swelling limits setting the lattice dimensions at about 15 nm. This limited swelling severely impairs their application as delivery vehicles of large drugs or as matrices for guiding protein crystallization. We report the discovery of self-assembly strategies leading to the emergence of lipid bicontinuous single crystals with unprecedented swelling capacity. The conventional strategy to increase unit cell size is tweaking membrane composition to include charged building blocks, a process to achieve electrostatic-driven swelling. In this paper, we demonstrate that controlling self-assembly external conditions when coupled to membrane composition yields 3D bicontinuous cubic phases that swell up to lattice dimensions of 68 nm. Importantly, and contrary to what is perceived for soft lyotropic materials in general, the self-assembly methodology enables the development of large super-swelled monocrystals. Utilizing small-angle X-ray scattering and cryoelectron microscopy, we underpin three crucial factors dictating the stabilization of super-swelled lipid bicontinuous cubic single crystals: () organic solvent drying speed, () membrane charge density, and () polyethylene glycol-conjugated lipids amount.

show abstract

Section: Significancesupporting

confidence: 90%

Super-swelled lyotropic single crystals

Kim

Song

Leal

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Next we performed similar MD simulations using the DLPE lipid bilayer system that mimics membrane surfaces2627. Two monomers were placed above and below the bilayer (Fig.…”

Section: Resultsmentioning

confidence: 99%

A novel pathway for amyloids self-assembly in aggregates at nanomolar concentration mediated by the interaction with surfaces

Banerjee

Hashemi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

A limitation of the amyloid hypothesis in explaining the development of neurodegenerative diseases is that the level of amyloidogenic polypeptide in vivo is below the critical concentration required to form the aggregates observed in post-mortem brains. We discovered a novel, on-surface aggregation pathway of amyloidogenic polypeptide that eliminates this long-standing controversy. We applied atomic force microscope (AFM) to demonstrate directly that on-surface aggregation takes place at a concentration at which no aggregation in solution is observed. The experiments were performed with the full-size Aβ protein (Aβ42), a decapeptide Aβ(14-23) and α-synuclein; all three systems demonstrate a dramatic preference of the on-surface aggregation pathway compared to the aggregation in the bulk solution. Time-lapse AFM imaging, in solution, show that over time, oligomers increase in size and number and release in solution, suggesting that assembled aggregates can serve as nuclei for aggregation in bulk solution. Computational modeling performed with the all-atom MD simulations for Aβ(14-23) peptide shows that surface interactions induce conformational transitions of the monomer, which facilitate interactions with another monomer that undergoes conformational changes stabilizing the dimer assembly. Our findings suggest that interactions of amyloidogenic polypeptides with cellular surfaces play a major role in determining disease onset.

show abstract

“…Firstly, it is important to mention that at no point in the preparation of the samples was there any effort to homogenise the particles' sizes. And yet, despite this heterogeneity, the delay time was shown to be reproducible with a peak in the probability at a non-zero value [18]. Secondly, our results shown in Fig.…”

Section: Resultsmentioning

confidence: 51%

“…a lamellar structure with liquid-like disorder in-plane. The phase change is accompanied by a change in morphology of the lipid particles, from faceted crystals to curved multi-lamellar vesicles (MLVs) [18]. The in-plane order-to-disorder transition is marked by the disappearance of the correlation peaks at wide scattering angles ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Delayed nucleation in lipid particles

et al. 2020

Self Cite

View full text Add to dashboard Cite

Metastable states in first-order phase-transitions have been traditionally described by classical nucleation theory (CNT). However, recently an increasing number of systems displaying such a transition have not been successfully modelled by CNT. The delayed crystallization of phospholipids upon super-cooling is an interesting case, since the extended timescales allow access into the dynamics. Herein, we demonstrate the controllable behavior of the long-lived metastable liquid-crystalline phase of dilauroyl-phosphatidylethanolamine (DLPE), arranged in multi-lamellar vesicles, and the ensuing cooperative transition to the crystalline state. Experimentally, we find that the delay in crystallization is a bulk phenomenon, which is tunable and can be manipulated to span two orders of magnitude in time by changing the quenching temperature, solution salinity, or adding a secondary phospholipid. Our results reveal the robust persistence of the metastability, and showcase the apparent deviation from CNT. This distinctive suppression of the transition may be explained by the resistance of the multi-lamellar vesicle to deformations caused by nucleated crystalline domains. Since phospholipids are used as a platform for drug-delivery, a programmable design of cargo hold and release can be of great benefit.

show abstract

Metastability in lipid based particles exhibits temporally deterministic and controllable behavior

Cited by 16 publications

References 30 publications

Super-swelled lyotropic single crystals

Super-swelled lyotropic single crystals

A novel pathway for amyloids self-assembly in aggregates at nanomolar concentration mediated by the interaction with surfaces

Delayed nucleation in lipid particles

Contact Info

Product

Resources

About