Membrane tension regulates motility by controlling lamellipodium organization

Abstract

Many cell movements proceed via a crawling mechanism, where polymerization of the cytoskeletal protein actin pushes out the leading edge membrane. In this model, membrane tension has been seen as an impediment to filament growth and cell motility. Here we use a simple model of cell motility, the Caenorhabditis elegans sperm cell, to test how membrane tension affects movement and cytoskeleton dynamics. To enable these analyses, we create transgenic worm strains carrying sperm with a fluorescently labeled cytoskeleton. Via osmotic shock and deoxycholate treatments, we relax or tense the cell membrane and quantify apparent membrane tension changes by the membrane tether technique. Surprisingly, we find that membrane tension reduction is correlated with a decrease in cell displacement speed, whereas an increase in membrane tension enhances motility. We further demonstrate that apparent polymerization rates follow the same trends. We observe that membrane tension reduction leads to an unorganized, rough lamellipodium, composed of short filaments angled away from the direction of movement. On the other hand, an increase in tension reduces lateral membrane protrusions in the lamellipodium, and filaments are longer and more oriented toward the direction of movement. Overall we propose that membrane tension optimizes motility by streamlining polymerization in the direction of movement, thus adding a layer of complexity to our current understanding of how membrane tension enters into the motility equation. I n crawling cells, motility is mainly driven by actin polymerization, which forms filaments beneath the leading edge cell membrane to make protrusions (1). In this scenario, polymerization is inhibited by the presence of the cell membrane, and membrane tension is thus commonly seen as an impediment to cell motility (2). Experiments show that lamellipodial extension rate is indeed inversely correlated with membrane tension (3), but steady-state, whole cell translocation has not been studied. Here we use a simplified system of crawling cell motility, the Caenorhabditis elegans sperm cell, in order to address the question of how membrane tension affects whole cell translocation. The sperm cell contains only cytoskeleton, mitochondria, and nuclear material and is incapable of de novo protein synthesis or classical exo-and endocytosis, thus representing a useful model for exploring the interplay between membrane tension and cell motility. The sperm cell translocates by adhering to the substrate and emitting a dynamic lamellipodia, in a manner that is morphologically similar to actomyosin containing motile cells, despite the fact that the movement of sperm cells is powered by the dynamics of the major sperm protein (MSP) cytoskeleton in the absence of actin and known molecular motors (4, 5).The production of fluorescently labeled actin in living cells was a watershed in the understanding of how actin structures assemble, flow, and disassemble to produce cell motility. However, due to efficient gene silencing mechanisms in th...

Shape Transformations of Lipid Bilayers Following Rapid Cholesterol Uptake

“…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.…”

Plasma membrane tension orchestrates membrane trafficking, cytoskeletal remodeling, and biochemical signaling during phagocytosis

“…1A and Movie S2). The only method to date to artificially increase membrane tension is to subject cells to hypotonic stress (12,13,23,24). Whereas it is not possible to totally exclude side effects on other signaling pathways, we did observe that replacing media with hypotonic solution at half tonicity clearly induced an increase in membrane tension in macrophages (Fig.…”

Cell migration: from tissue culture to embryos

“…4C,bottom) proposes that chemoattractants simply bias the dynamic and self-organising autocatalytic nature of protrusions towards the gradient without the need of a compass (Arrieumerlou and Meyer, 2005;Insall, 2010). As such, this model seems to better integrate recent data showing that membrane tension resulting from actin polymerisation acts as a longrange physical signal that inhibits protrusion formation in regions other than the cell front (Batchelder et al, 2011;Houk et al, 2012). Although the compass and chemotactic bias models may differ in some aspects, it should be noted that they are not mutually exclusive and thus both probably operate in most eukaryotic cells (Insall, 2013).…”