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

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

15.6.3.1 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 DeltaV_cell from the original cell volume V_cell is related to the change in plasma membrane area DeltaA_cell of an unstretched membrane of area A_cell by the relations DeltaV_cell /V_cell ~ ((1 + DeltaA_cell/A_cell)^3/2 - 1) and DeltaA_cell/A_cell = T_memb / K_memb, where T_memb is the isotropic tension due to membrane expansion, the area compressibility modulus K_memb = 0.378 N/m for erythrocyte plasma membrane at 310 K, and K_memb = 0.636 N/m for leukocyte plasma membrane (Section 9.4.3.2.1). Taking a conservative lysis limit of T_memb ~ 4 x 10^-3 N/m for erythrocytes, then DeltaV_cell/V_cell ~ 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 T_memb = 1.7 N/m and K_memb = 1.3 N/m for TB/C3 hybridoma cells and T_memb = 1.8 N/m and K_memb = 1.2 N/m for NS1 myeloma cells [4530], then DeltaV_cell /V_cell ~ 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 DeltaV_cell /V_cell ~ 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 DeltaV_cell /V_cell ~ 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