Nanomedicine, Volume IIA: Biocompatibility

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

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003 Membrane Elasticity and Cellular Expansion

The introduction of foreign material into a cell may cause intracellular volume to expand. Assuming a spherical cell shape, the change in cell volume DeltaVcell from the original cell volume Vcell is related to the change in plasma membrane area DeltaAcell of an unstretched membrane of area Acell by the relations DeltaVcell /Vcell ~ ((1 + DeltaAcell/Acell)3/2 - 1) and DeltaAcell/Acell = Tmemb / Kmemb, where Tmemb is the isotropic tension due to membrane expansion, the area compressibility modulus Kmemb = 0.378 N/m for erythrocyte plasma membrane at 310 K, and Kmemb = 0.636 N/m for leukocyte plasma membrane (Section Taking a conservative lysis limit of Tmemb ~ 4 x 10-3 N/m for erythrocytes, then DeltaVcell/Vcell ~ 1.6% for red cells and ~0.9% for white cells. However, erythrocytes are not spheres but biconcave disks [3967] with a mean volume of 94 micron3 in isotonic solution (300 mosmol). They absorb water in hypotonic solution, becoming spherical at 131 mosmol with a volume of 164 micron3, demonstrating a capacity for volumetric expansion of 74% without losing membrane integrity (albeit with some loss of rheological functionality). Other cells may tolerate even greater expansion. For example, taking Tmemb = 1.7 N/m and Kmemb = 1.3 N/m for TB/C3 hybridoma cells and Tmemb = 1.8 N/m and Kmemb = 1.2 N/m for NS1 myeloma cells [4530], then DeltaVcell /Vcell ~ 250% for hybridomas and ~300% for myelomas. These estimates are crude at best because the lipid population of the plasma membrane is constantly changing and may enlarge or contract over time [4641, 4642].

For more than four decades, microbiologists have routinely extracted or inserted an entire nucleus into a cell using micropipettes without compromising cell viability [4531]. Such nuclear transplantation represents a volumetric change of DeltaVcell /Vcell ~ 3.4% for the typical 20-micron human tissue cell (Table 8.17) but in the case of a human leukocyte would represent a volumetric change of DeltaVcell /Vcell ~ 18% for an eosinophil, 22% for a neutrophil, 26% for a monocyte, or 51% for a lymphocyte [4532]. Decades of laboratory practice have confirmed that at least ~100 micron3/cell of foreign material (representing perhaps 1-3% of cell volume) can be safely injected into a somatic cell without any significant effect on cell viability [4533].

Neutrophils increase in volume by ~15% when stimulated in suspension, and rabbit neutrophils that migrate into the abdominal wall (150 micron3) are +50% larger than those in the abdominal wall vasculature (100 micron3). Human neutrophils induced by fMLP to migrate into collagen gels (290 micron3) are 42% larger than those that did not migrate (204 micron3) [4534].


Last updated on 30 April 2004