**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

**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 micron^{3} in isotonic solution (300 mosmol).
They absorb water in hypotonic solution, becoming spherical at 131 mosmol with
a volume of 164 micron^{3}, 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 micron^{3}/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
micron^{3}) are +50% larger than those in the abdominal wall vasculature
(100 micron^{3}). Human neutrophils induced by fMLP to migrate into
collagen gels (290 micron^{3}) are 42% larger than those that did not
migrate (204 micron^{3}) [4534].

Last updated on 30 April 2004