Plasma Membrane Disruption: Repair, Prevention, Adaptation

Abstract

Many metazoan cells inhabit mechanically stressful environments and, consequently, their plasma membranes are frequently disrupted. Survival requires that the cell rapidly repair or reseal the disruption. Rapid resealing is an active and complex structural modification that employs endomembrane as its primary building block, and cytoskeletal and membrane fusion proteins as its catalysts. Endomembrane is delivered to the damaged plasma membrane through exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or, when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption also can be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.

Transient elastohydrodynamic drag on a particle moving near a deformable wall

“…7) well in excess of the 2-3% range sufficient to cause transient rupture of the plasma membrane (58). Although cells have the capacity to reseal damaged plasma membranes very rapidly (42), sufficiently large strains are likely to induce permanent cell damage. Recent experiments (4,35) showed that the damage to epithelial cells in a flow chamber due to the passage of a bubble at very low capillary numbers correlates with normal-stress (pressure) gradients rather than shear stress, shear-stress gradients, or the time of exposure to stress.…”

Hypercapnic Acidosis Impairs Plasma Membrane Wound Resealing in Ventilator-injured Lungs

“…The molecular mechanisms that drive plasma membrane resealing vary with cell type and lesion size (28). Small plasma mem-brane wounds (Ͻ 1 m) tend to seal spontaneously by lateral plasma membrane lipid flow.…”

“…This is in keeping with data suggesting that removal of mechanical stress causes a rapid restoration of vascular barrier function (24-26). In cell culture failure to reseal a plasma membrane break causes cell death by necrosis, whereas a wounded and resealed cell remains viable for some time (27,28).The objective of the experiments described in this article was to assess the effects of CO 2 on lung cell injury and repair in an experimental model of VILI as well as in cell culture. The VILI model is the isolated perfused rat lung preparation as described by Gajic and coworkers (23), in which effect centers on the assessment of cell injury in subpleural airspaces, using confocal microscopy.…”

“…This is in keeping with data suggesting that removal of mechanical stress causes a rapid restoration of vascular barrier function (24-26). In cell culture failure to reseal a plasma membrane break causes cell death by necrosis, whereas a wounded and resealed cell remains viable for some time (27,28).…”

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

“…Recently, defects in post-translational glycosylation of membrane proteins have been shown to be causative factors in muscle-eye-brain disease, Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, congenital muscular dystrophy type 1C, and limb-girdle muscular dystrophy type 2I (6 -8). In most mammalian tissues, plasma membrane disruption is a common form of injury due to mechanical stress, and resealing of the damaged membrane is critical for cell survival (9,10). In skeletal muscle, disruptions of the membrane are more frequent due to the repeated lengthening and shortening of muscle cells during contraction (11).…”