INFINA (EX INFIP)   05545
INSTITUTO DE FISICA INTERDISCIPLINARIA Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Nanoscale transport through permeabilizing structures in electrically stressed cell membranes
Autor/es:
CASTELLANI F ; VERNIER PT; FERNÁNDEZ ML; SÖZER EB; RISK M
Reunión:
Simposio; 15 th International Bioelectrics Symposium (BIOELECTRICS 2018), Prague, Czech Republic, 23-26 September 2018; 2018
Resumen:
Despite broad agreement that the pulsed-electric-field-induced permeabilization of cell membranes involves more than the creation of lipid pores [1], reports of efforts to model and to investigate experimentally the complexity of the transport structures in the electropermeabilized cell cf. Fig. 4 in [2]) are difficult to find. Here we discuss progress toward characterizing the permeabilizingstructures and processes (electropermeasomes) that make up the electropermeome [3]. Molecular simulations of ion and small molecule transport through lipid electropores provide estimates of single pore conductance and the corresponding pore lifetimes and areal pore densities needed to align the properties of lipid pores with material transport observed in experiments. Although these correlations are useful for calibrating molecular and continuum models with laboratory observations, the lifetimes of lipid pores in molecular models (< 1 μs) aremuch too short to account for the persistent permeabilization (>> 1 s) that follows exposure of cells to pulsed electric fields. To account for this, we propose a set of hypothetical permeabilizing structures, including evolved lipid pores, electro-modified membrane proteins,and other components of the stressed membrane, with pathways to experimental validation.New molecular simulations of interactions of ions with lipid pore walls that may contribute to pore evolution are described, and results with mechanically constrained pores with long lifetimes are introduced for the first time.Recent experimental data present new inconsistentencies with the implicitly passive cell represented in the standard model of electroporation. A simple explanation is offered for the very different transport patterns observed for cationic and anionic small fluorescent molecules after electropermeabilization. Electrically stressed cells, even though their membrane barrier function has been compromised, restore a non-zero resting potential very quickly after electroporating pulse exposures. Permeabilized cells fight back![1] Sabri, N., B. Pelissier, and J. Teissié. 1996. Electropermeabilization of intact maize cells induces an oxidative stress. Eur. J. Biochem. 238:737-743.[2] Pakhomova, O. N., B. W. Gregory, V. A. Khorokhorina, A. M. Bowman, S. Xiao, and A. G. Pakhomov. 2011. Electroporation-induced electrosensitization. PLoS ONE 6:e17100.[3] Sözer, E. B., Z. A. Levine, and P. T. Vernier. 2017. Quantitative limits on small molecule transport via the electropermeome ? Measuring and modeling single nanosecond perturbations. Sci. Rep. 7:57