- PAR ID:
- 10304061
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 17
- Issue:
- 36
- ISSN:
- 1744-683X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
null (Ed.)Cellular membranes are elastic lipid bilayers that contain a variety of proteins, including ion channels, receptors and scaffolding proteins. These proteins are known to diffuse in the plane of the membrane and to influence the bending of the membrane. Experiments have shown that lipid flow in the plane of the membrane is closely coupled with the diffusion of proteins. Thus, there is a need for a comprehensive framework that accounts for the interplay between these processes. Here, we present a theory for the coupled in-plane viscous flow of lipids, diffusion of transmembrane proteins and elastic deformation of lipid bilayers. The proteins in the membrane are modelled such that they influence membrane bending by inducing a spontaneous curvature. We formulate the free energy of the membrane with a Helfrich-like curvature elastic energy density function modified to account for the chemical potential energy of proteins. We derive the conservation laws and equations of motion for this system. Finally, we present results from dimensional analysis and numerical simulations and demonstrate the effect of coupled transport processes in governing the dynamics of membrane bending and protein diffusion.more » « less
-
Membrane bending is a ubiquitous cellular process that is required for membrane traffic, cell motility, organelle biogenesis, and cell division. Proteins that bind to membranes using specific structural features, such as wedge-like amphipathic helices and crescent-shaped scaffolds, are thought to be the primary drivers of membrane bending. However, many membrane-binding proteins have substantial regions of intrinsic disorder which lack a stable three-dimensional structure. Interestingly, many of these disordered domains have recently been found to form networks stabilized by weak, multivalent contacts, leading to assembly of protein liquid phases on membrane surfaces. Here we ask how membrane-associated protein liquids impact membrane curvature. We find that protein phase separation on the surfaces of synthetic and cell-derived membrane vesicles creates a substantial compressive stress in the plane of the membrane. This stress drives the membrane to bend inward, creating protein-lined membrane tubules. A simple mechanical model of this process accurately predicts the experimentally measured relationship between the rigidity of the membrane and the diameter of the membrane tubules. Discovery of this mechanism, which may be relevant to a broad range of cellular protrusions, illustrates that membrane remodeling is not exclusive to structured scaffolds but can also be driven by the rapidly emerging class of liquid-like protein networks that assemble at membranes.
-
Accumulation of protein-based (Aβ) aggregates on cellular membranes with varying structural properties is commonly recognized as the key step in Alzheimer's pathogenesis. But experimental and computational challenges have made this biophysical characterization difficult. In particular, studies connecting biological membrane organization and Aβ aggregation are limited. While experiments have suggested that an increased membrane curvature results in faster Aβ peptide aggregation in the context of Alzheimer's disease, a mechanistic explanation for this relation is missing. In this work, we are leveraging molecular simulations with a physics-based coarse grained model to address and understand the relationships between curved cellular membranes and aggregation of a model template peptide Aβ 16–22. In agreement with experimental results, our simulations also suggest a positive correlation between increased peptide aggregation and membrane curvature. More curved membranes have higher lipid packing defects that engage peptide hydrophobic groups and promote faster diffusion leading to peptide fibrillar structures. In addition, we curated the effects of peptide aggregation on the membrane's structure and organization. Interfacial peptide aggregation results in heterogeneous headgroup–peptide interactions and an induced crowding effect at the lipid headgroup region, leading to a more ordered headgroup region and disordered lipid-tails at the membrane core. This work presents a mechanistic and morphological overview of the relationships between the biomembrane local structure and organization, and Aβ peptide aggregation.more » « less
-
Abstract Certain proteins have the propensity to bind to negatively curved membranes and generate negative membrane curvature. The mechanism of action of these proteins is much less studied and understood than those that sense and generate positive curvature. In this work, we use implicit membrane modeling to explore the mechanism of an important negative curvature sensing and generating protein: the main ESCRT III subunit Snf7. We find that Snf7 monomers alone can sense negative curvature and that curvature sensitivity increases for dimers and trimers. We have observed spontaneous bending of Snf7 oligomers into circular structures with preferred radius of ~20 nm. The preferred curvature of Snf7 filaments is further confirmed by the simulations of preformed spirals on a cylindrical membrane surface. Snf7 filaments cannot bind with the same interface to flat and curved membranes. We find that even when a filament has the preferred radius, it is always less stable on the flat membrane surface than on the interior cylindrical membrane surface. This provides an additional energy for membrane bending which has not been considered in the spiral spring model. Furthermore, the rings on the cylindrical spirals are bridged together by helix 4 and hence are extra stabilized compared to the spirals on the flat membrane surface.
-
Atomistic molecular dynamics simulations of concentrated protein solutions in the presence of a phospholipid bilayer are presented to gain insights into the dynamics and interactions at the cytosol–membrane interface. The main finding is that proteins that are not known to specifically interact with membranes are preferentially excluded from the membrane, leaving a depletion zone near the membrane surface. As a consequence, effective protein concentrations increase, leading to increased protein contacts and clustering, whereas protein diffusion becomes faster near the membrane for proteins that do occasionally enter the depletion zone. Since protein–membrane contacts are infrequent and short-lived in this study, the structure of the lipid bilayer remains largely unaffected by the crowded protein solution, but when proteins do contact lipid head groups, small but statistically significant local membrane curvature is induced, on average.more » « less