© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.5.7.2.1 Natural Cell Membrane Wounding

Plasma membrane disruptions appear to be a common occurrence in cells residing in tissues such as gut and skin that are normally exposed to mechanical stress in vivo [4227]. Experimentally, animal locomotion transiently wounds the plasma membranes of various cells of skin, which allows otherwise impermeant tracer molecules to enter and be trapped in the cytoplasm. One study [4227] produced an estimate that the epidermis of digits from actively locomoting animals is composed of 10.5% wounded cells, vs. 3.7% wounded cells for quiescent animals. Wounded fibroblasts, glandular cells, and endothelial cells were also seen in mechanically stressed skin [4227]. Scrape wounding of epithelial cells activates repair-related gene expression inside the cell [4228].

Exercise causes membrane damage in muscle cells (e.g., rat muscle fiber cells or myocytes [4229]) and red blood cells (Section 15.5.5.1.1), and dystrophic muscle cells are especially susceptible [4230]. The plasma membrane of cardiac myocytes can be wounded by vigorous cell contraction or by vascular pressure overloading (e.g., via aortic banding which produces abnormally high hemodynamic loads [4231]). The percentage of rat aortic endothelial cells found to be naturally wounded varies considerably between individual animals from 1.4-17.9% (mean 6.5%) [3923]. Wounded endothelial cells are heterogeneously distributed, being found in distinct clusters either in the shape of streaks aligned with the long axis of the vessel or in the shape of partial or complete rims surrounding bifurcation openings such as the ostia of the intercostal arteries [3923]. However, physical exercise (running) and spontaneous hypertension may not produce an increased frequency of aortic endothelial cell membrane wounding [3923].

Cells can also be mechanically damaged simply by rough handling. For example, passing cells back and forth through a standard syringe needle or similar narrow orifice causes transient membrane disruptions [4232], and each trip through a 14-gauge blood dialysis needle at a 2.2 m/sec peak velocity damages 0.1% of red cells near the needle wall [3690]. Mechanical forces from tape stripping or needle puncture also transiently wounds the plasma membranes of various skin cells, though these cells can survive such wounding [4227]. Nanorobots located on membrane surfaces could be manipulated via external fields to flex [3971] or even to perforate those surfaces. In one proposal [4233], MAb-complexed ferrofluid particles selectively bound to the surfaces of virus-infected cells would be rapidly vibrated using an external magnetic field, causing the bound particles to perforate the cell membranes of the infected cells or to damage their intracellular structures, leading to targeted cell lysis. However, neurons can survive patch clamp experiments which may involve suction and mechanical pinching of 30-100 micron² cell membrane areas for experiments lasting up to ~1 week in duration [4234]; note that cytoskeleton-free lipid bilayer tethers have been mechanically drawn from the plasma membrane of erythrocytes (~40 nm wide tethers) [5659], neurons (~200 nm wide) [5660], and neutrophils [5661].

Last updated on 30 April 2004