tools for the electromanipulation of the interior of the biological cells – INTCELL

The electric pulses used until now have effects focused exclusively at the level of the external membrane of the cells. These effects (in particular cells electroporation) are used in routine in biology and in medicine (for example, in the case of the antitumor electrochemotherapy). Recently, another type of electric pulses began to be used: pulses of a duration from 10 till 300 nanoseconds, of strong field amplitude (10 to 150 kV/cm). These pulses have effects at the level of the external membrane but also at the level of the cell internal membranes. INTCELL will be interested in the theoretical and experimental study of the effects of pulses of duration equal or lower than 10 ns which could have preferential effects on the internal membranes of cells. The theoretical study, that will be carried out by partners 3 and 4, will be devoted to the description by molecular dynamics of the changes which these pulses can provoke at the level of membranes. It will also concern the elaboration of mathematical models allowing to describe the microdosimetry of the electric fields generated inside the cell by these pulses. It will allow to emit hypotheses on the electric parameters of these pulses allowing to modify the membrane of the intracellular organelles (nucleus, mitochondria, vesicles) in a specific way. These hypotheses will be experimentally estimated. The partner 1 is one of world experts in the conception of generators capable of delivering electric pulses of less than 10 ns and of an amplitude of several to several tens of kilovolts. It will supply the devices capable of delivering the impulses anticipated by the theoretical approach, but also answering the constraints of the biology, supplied by partner 2. This last one already has an experience in the exposure of cells to this type of pulses and in the constraints of the systems of exposure. It has already put in evidence effects of these pulses (subjected to publication). Within the framework of INTCELL the partner 2 will estimate biological effects on the nucleus, the vesicles or the mitochondria resulting from a specific effect of well defined pulses. INTCELL is thus a complex interdisciplinary study intended to develop: new molecular models of the disturbance of the biological membranes exposed to ultrashort electric pulses with a strong frequency content; new cellular models of the disturbance of biological cells exposed to these pulses; new pulse generators capable of delivering these pulses; and the carrying out of the experimental studies allowing to demonstrate the specific manipulation of the membrane of certain intracellular organelles, by being capable of provoking specific physiological reactions of the cells exposed to the electric pulses. INTCELL also tends to build the link missing between the molecular and macroscopic scales, to end in a multi-scale model describing in a more rigorous way the local effects of an electromagnetic field applied to the biological cells. INTCELL, that combines aspects in silico, aspects of technological development and aspects of biological experimentation, is a very original and ambitious project, but he gathers the best French experts in the domain allowing to perform such an interdisciplinary project.