Objective Populations of fibroblasts and related cells of mesenchymal tissues in vivo, include several subtypes expressing different isoforms of actins, especially the cells expressing or non-expressing a-smooth muscle actin (a-SM-positive and a-SM-negative cells). The aim of this project is to review and analyze the mechanisms determining different molecular and structural organization of focal adhesions in cells with various isoforms of actin.This analysis will be based on the hypothesis is that the main differences between these isotypes are manifested by various expression of functions related to contractility of cortical cytoskeleton and mechanochemical interactions of these cells with the extracellular matrix. Cell shape, organization of focal adhesions with the matrix, pseudopodial activity of motile cells and traction exerted by these cells on the elastic substrata, will be compared in the a-SM-positive and a-SM-negative cells from several types of fibroblastic cultures. Reactions of a-SM-positive and a-SM-negative cells to the chemically and geometrically different substrata to which these cells will be attached will be examined. Expression of a-SM actin will be induced by cytokines (e.g. TGFb). Polymerization of a-SM actin will be selectively inhibited by the introduction into the cells of specific N-terminal decapeptide and alterations of cell characteristics induced by this inhibition will be examined. Preliminary data suggest that expression of a-SM actin increases contractility of actin cytoskeleton of fibroblasts, alters their adhesiveness and motility and in this way alters their relationships with the substrata of various compositions and shapes. The results of this project will reveal possible new molecular mechanisms of cytoskeleton contractility regulation and of cell-matrix relations, by changing the expression of various actin isoforms. These mechanisms may play a major role in normal morphogenesis and in its pathologic alterations, especially, in those accompanying neoplastic transformations. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Topic(s) 4 - Life Sciences INTAS - INTAS Call for proposal Data not available Funding Scheme Data not available Coordinator Universite de Geneve EU contribution No data Address Rue Michel-Servet, 1 1211 Geneva 4 Switzerland See on map Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all M.V. Lomonosov Moscow State University Russia EU contribution No data Address Vorobievy Gory 119 899 Moscow See on map Total cost No data Russian Academy of Medical Sciences Russia EU contribution No data Address Kashirskoje shosse, 24 115478 Moscow See on map Total cost No data Universite Victor Segalen Bordeaux 2 France EU contribution No data Address Rue Leo-Saignat, 146 33076 Bordeaux Cedex See on map Total cost No data
