Repairing a torn cell surface

Since the advent of microsurgical techniques in the early part of the last century, it has been known that animal cells can survive the experimental creation of very large holes (>1000 μm2) in their surface (reviewed in Chambers and Chambers, 1961; Heilbrunn, 1956). Remarkably, these initial observations of a truly remarkable cell capacity failed, for many subsequent decades, to generate further interest. This neglect had two causes. First, with the widespread use of microinjection and other methods for breaching the cell surface, resealing came to be associated primarily with the laboratory setting rather than with any natural, biological one. Resealing permitted cells to survive a microneedle puncture and was therefore a very useful cell property. It was, however, apparently of little biological interest, because a disruption, it was obvious, was merely a laboratory-generated artifact. Considerable work, which is briefly reviewed here, has clearly demonstrated that the mammalian body, in common with other machines that have moving parts, is not immune under normal operating conditions from mechanically induced wear and tear. Plasma membrane disruption is a common and normal event in many mechanically active mammalian tissues, and so resealing, because it permits cells to survive this injury, is a response that has fundamental biological significance. In addition to suffering from a kind of ‘guilt by association’, resealing languished for a second reason. It was thought to have a simple and trivial explanation. Thus, once it was established that the principal cell surface barrier torn by the microneedle was a fluid lipid bilayer, resealing became explicable as simply the thermodynamically determined outcome of the well established principle that ‘Membranes hate edges’ (Parsegian et al., 1984). According to this view, still current in textbooks, resealing is an ability inherent in all membranes, a response requiring nothing more than that the torn membrane to be held at a temperature above its liquid-crystalline transition point. This view is no longer tenable, at least in the case of large (>1 μm) disruptions occurring in nucleated animal cells. Rather, as outlined here, resealing is now viewed as the outcome of a dynamic and complex mechanism, one that relies heavily on the participation of numerous cytoplasmic constituents. Recent work, discussed below, strongly implicates lysosomes and the actin-based cytoskeleton as two key cytoplasmic players in the resealing response and actin/myosin-based contraction in the subsequent repair of wound-associated damage to the cell cortex.