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• Surface Charge of Giant Axons of Squid and Lobster

  Surface Charge of Giant Axons of Squid and Lobster Biophysical Journal, Volume 8, Issue 4, 1 April 1968, Pages 470-489 John R. Segal Abstract A method is described for the determination of the electrophoretic mobility of single, isolated, intact, giant axons of squid and lobster. In normal physiological solutions, the surface of hydrodynamic shear of these axons is negatively charged. The of the estimated surface charge density is -1.9×10 coul cm for squid axons, -4.2×10 coul cm for lobster axons. The electrophoretic mobility of squid axons decreases greatly when the applied transaxial electric field is made sufficiently intense; action potential propagation is blocked irreversibly by transaxial electric fields of the same intensity. The squid axon recovers its mobility hours later and is then less affected by transaxial fields. Eventually, a state is reached in which the transaxial field irreversibly reverses the sign of the surface charge. In contrast, there is no obvious effect of electric field on the mobility of lobster axons. The mobility of lobster axons becomes undetectable in the presence of Th at a concentration which blocks the action potential, and in the presence of La at a concentration which does not affect propagation. Quinine does not alter lobster axon mobility at a concentration which blocks action potential conduction. Replacement of extracellular Na by K is without effect upon lobster axon mobility. The electrophysiological implications of the results are discussed. Abstract | PDF (1252 kb)

• Modeling Transmembrane Transport through Cell Membrane Wound...

  Modeling Transmembrane Transport through Cell Membrane Wounds Created by Acoustic Cavitation Biophysical Journal, Volume 95, Issue 9, 1 November 2008, Pages 4124-4138 Vladimir Zarnitsyn, Christina A. Rostad and Mark R. Prausnitz Abstract Cells exposed to acoustic cavitation and other mechanical stresses can be transiently permeabilized to permit intracellular uptake of molecules, including drugs, proteins, and genes. Microscopic imaging and other studies suggest that intracellular loading occurs through plasma membrane wounds of submicrometer radius that reseal over time through the aggregation and fusion of lipid vesicles trafficked to the wound site. The goal of this study was to 1), determine the size of membrane wounds as a function of time after in vitro sonication of DU145 prostate cancer cells under conditions that caused extensive acoustic cavitation; and 2), theoretically model transport processes leading to intracellular loading. Our overall hypothesis was that intracellular loading is governed by passive diffusion through porous membrane wounds of up to 300-nm radius containing pores that permit entry of molecules up to at least 28-nm radius over a timescale of minutes. Experimental measurements showed intracellular loading of molecules with radii from 0.6 to 28nm, where most loading occurred after sonication over a timescale up to minutes and where smaller molecules were taken up to a greater extent and over a longer timescale than larger molecules. Theoretical modeling predicted that membrane wounds would have a 300-nm radius initially and then would shrink, with a half life of 20 to 50s. Uptake was shown to occur predominantly by diffusion and the increasing levels of uptake with decreasing molecular size was explained primarily by differences in molecular diffusivity and, for the largest molecule, geometrical hindrance within the wound. Mathematical modeling was simplified, because transport through porous wounds of possibly complex internal nanostructure was governed largely by transport at the edge of the wound, and depended only weakly on the size, number, and distribution of nanopores within the wound under the conditions relevant to this study. Overall, this study developed a theoretical framework for analysis of transmembrane transport through cell membrane wounds and thereby provided quantitative estimates of their size and lifetime. Abstract | Full Text | PDF (302 kb)

• Effect of cell arrangement and interstitial volume fraction ...

  Effect of cell arrangement and interstitial volume fraction on the diffusivity of monoclonal antibodies in tissue Biophysical Journal, Volume 64, Issue 5, 1 May 1993, Pages 1638-1646 A.W. el-Kareh, S.L. Braunstein and T.W. Secomb Abstract We present theoretical calculations relating the effective diffusivity of monoclonal antibodies in tissue (Deff) to the actual diffusivity in the interstitium (Dint) and the interstitial volume fraction phi. Measured diffusivity values are effective values, deduced from concentration profiles with the tissue treated as a continuum. By using homogenization theory, the ratio Deff/Dint is calculated for a range of interstitial volume fractions from 10 to 65%. It is assumed that only diffusion in the interstitial spaces between cells contributes to the effective diffusivity. The geometries considered have cuboidal cells arranged periodically, with uniform gaps between cells. Deff/Dint is found to generally be between (2/3) phi and phi for these geometries. In general, the pathways for diffusion between cells are not straight. The effect of winding pathways on Deff/Dint is examined by varying the arrangement of the cells, and found to be slight. Also, the estimates of Deff/Dint are shown to be insensitive to typical nonuniformities in the widths of gaps between cells. From our calculations and from published experimental measurements of the effective diffusivity of an IgG polyclonal antibody both in water and in tumor tissue, we deduce that the diffusivity of this molecule in the interstitium is one-tenth to one-twentieth its diffusivity in water. We also conclude that exclusion of molecules from cells (an effect independent of molecular weight) contributes as much as interstitial hindrance to the reduction of effective diffusivity, for small interstitial volume fractions (around 20%). This suggests that the increase in the rate of delivery to tissues resulting from the use of smaller molecular-weight molecules (such as antibody fragments or bifunctional antibodies) may be less than expected. Abstract | PDF (852 kb)

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Abstract

Light-scattering/intensity autocorrelation measurements of vesicle diffusivity were used to follow the time course of the osmotic response of lobster abdominal sarcoplasmic reticulum vesicles to five lipophobic nonelectrolytes. Steady-state portions of the resulting time traces show these vesicles to be permeable to ethylene glycol and glycerol and impermeable to erythritol, glucose, and sucrose. Using measured values of the hydrodynamic radii of these nonelectrolytes, it is concluded that under passive transport conditions, these vesicles may be thought of as having pores whose radii lie between 3.1 and 3.5 A. In addition, the results presented here indicated that above a certain impermeable nonelectrolyte concentration, vesicles did not respond osmotically even though they had not collapsed. This suggests that at least under the experimental conditions reported here, vesicles behaved as if rigid when their average volume had decreased to about 50% of its original isotonic value.