Modeling transmembrane transport through cell membrane wounds created by acoustic cavitation Export

@article{citeulike:3078124, 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 sub-micron 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 (i) 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 (ii) 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 28 nm, 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 membrane wounds to have a 300 nm radius initially and then to shrink with a half life of 20 to 50 s. 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. 10.1529/biophysj.108.131664}, author = {Zarnitsyn, Vladimir G. and Rostad, Christina A. and Prausnitz, Mark R.}, citeulike-article-id = {3078124}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.108.131664}, citeulike-linkout-1 = {http://www.biophysj.org/cgi/content/abstract/95/9/4124}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18676653}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18676653}, day = {1}, doi = {10.1529/biophysj.108.131664}, journal = {Biophys. J.}, keywords = {acoustic, cavitation, cell, defects, difffusion, loading, membrane, zarnit08pdf}, month = {August}, pages = {biophysj.108.131664+}, posted-at = {2008-08-03 02:58:52}, priority = {2}, title = {Modeling transmembrane transport through cell membrane wounds created by acoustic cavitation}, url = {http://dx.doi.org/10.1529/biophysj.108.131664}, year = {2008} }

TY - JOUR ID - citeulike:3078124 L3 - citeulike-article-id:3078124 N2 - 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 sub-micron 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 (i) 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 (ii) 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 28 nm, 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 membrane wounds to have a 300 nm radius initially and then to shrink with a half life of 20 to 50 s. 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. 10.1529/biophysj.108.131664 JF - Biophys. J. TI - Modeling transmembrane transport through cell membrane wounds created by acoustic cavitation SP - biophysj.108.131664 KW - acoustic KW - cavitation KW - cell KW - defects KW - difffusion KW - loading KW - membrane KW - zarnit08pdf AU - Zarnitsyn, Vladimir AU - Rostad, Christina AU - Prausnitz, Mark PY - 2008/08/01/ UR - http://dx.doi.org/10.1529/biophysj.108.131664 ER -