Physical principles of membrane remodelling during cell mechanoadaptation

Abstract

Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope—the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell–substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.

Shape Transformations of Lipid Bilayers Following Rapid Cholesterol Uptake

“…The latter is supported by our analogous findings with mechanically strained CSLBs (23,35). A similar mechanism is very likely to play a role in biological membranes (continuous and actin-supported), as demonstrated by a recent study on adherent cells subject to mechanical compression (36). After the initial uptake of cholesterol, we observe a decrease in the membrane surface area in all three model systems, evidenced by patch contraction, shrinking of membrane protrusions in CSLBs, or a decrease in the GUV radius.…”

“…For example, activation of signaling pathways in cells and cytoskeletal remodeling observed after incubation of cells with MbCD-Chol (6,7,38,39) are likely triggered by the non-specific increase in the membrane area, and thus a decrease in membrane tension, rather than by cholesterol itself. This suggestion is supported by recent studies that demonstrate the strong interplay between the membrane tension and the remodeling of the cell membrane and cytoskeleton (36,40,41). Finally, our work shows that MbCD-Chol should be used with caution as a cholesterol donor in cell and synthetic membrane studies, as the cyclodextrin may also extract a significant amount of phospholipids, thus inducing a variety of unexpected membrane responses, the mechanisms of which would require further investigation.…”

Hydraulic fracturing in cells and tissues: fracking meets cell biology

“…Instead, the authors showed that intercellular cracks originated from a build-up of hydraulic pressure at the ECM-cell interface. Interestingly, a similar behavior was observed in single cells seeded on a deformable hydrogel [28]. Here, the poroelastic flows confined to the cell-substrate interface produced membrane delamination and formation of inward bleb-like structures.…”

Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations

“…We show that in polarized cells these membrane invaginations and actin-rich structures co-localize at the cell front and assume that their rapid release in the course of bleb expansion can be considered passive as shown in in vitro setting in a different context (Kosmalska et al, 2015). The local association between invaginations and the actin could be extended to a functional link, as disruption of Cdc42 adversely affects membrane invagination formation and culminates in abnormal cell shape and impaired migration.…”