Membrane curvature in cell biology: An integration of molecular mechanisms

Abstract

Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists.

Gaussian curvature directs the distribution of spontaneous curvature on bilayer membrane necks

“…Spontaneous curvature of lipid bilayers can be produced by a variety of relatively well understood mechanisms 18,21,22 . In particular, the insertion of amphipathic α-helix into lipid bilayers is known to induce curvature and is involved in several neck formation processes.…”

“…Despite this diversity, their formation is subject to biophysical constraints, and most often requires bending the membrane in the presence of compositional in-plane heterogeneities. These membranes heterogeneities can be produced in many ways, resulting in a preferred mean curvature known as the spontaneous curvature [18][19][20][21][22] . The mechanisms inducing spontaneous curvature on the membrane can broadly be classified into five categories: lipid asymmetry across the leaflets, hydrophobic insertion due to proteins, scaffolding due to proteins, oligomerization, and crowding due to proteins or other external moieties.…”

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology

“…Curvature can also be generated by insertion of proteins like caveolin into one monolayer or surface association of intrinsically curved proteins that belong to the Bin, Amphiphysin and Rvs families [81]. K2P channel gating is modulated by lipid composition [44, 82], and reconstituted Piezo channels in lipid vesicles were activated by LPC (positive curvature generator) addition to the cytoplasmic monolayer [52].…”

Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR

“…Understanding the molecular mechanisms of these interactions is, therefore, of great importance. In the recent past, many proteins have been identified that can remodel membranes by their interplay with various cellular membranes [4, 5]. These include protein families like BIN/Amphiphysin/Rvs (BAR) [6–8], Eps 15-homology [9, 10], epsin [11], synaptotagmins [12] and synucleins [13–15].…”

“…This mechanism arises from the expansion of the total area of one membrane leaflet compared to the other [4, 5, 18, 19, 24]. Using these and/or quite possibly other mechanisms such as molecular crowding of protein on membrane, partitioning of shaped transmembrane domains, and cytoskeleton-mediated ‘pulling and pushing’ of membrane, a variety of membrane morphologies like small vesicles, tubular structures, membrane protrusions and lipoprotein particles are generated and have been observed in vivo [4, 5, 18, 19, 24, 25]. Interestingly, a single protein, for example α-synuclein, can also generate different lipid morphologies in vitro , even by just modulating the protein-to-lipid ratio (Fig.…”