Main description:

The genetic information contained in a cell needs the appropriate environment to express itself, not only the intracellular environment but also the extracel- lular one. The latter is provided to a great extent by the molecules which constitute the extracellular matrix. On the one hand, the matrix creates inter alia the right pH and osmotic envi- ronment and allows the diffusion of messengers targeting the cell membrane; on the other hand, it has a mechanical effect whose relevance began to be understood 28 years ago. Basically, the messages that reach the cell and are then transported to the genome depend on molecular conformational flexibility. Molecular structures usually prevail because they represent states of minimum potential energy cre- ating energy barriers which are activated through conformational changes. From the periphery to the nucleus the information flows through the activa- tion of energy barriers. The tools used to switch from low-energy to high- energy molecular configurations are: the binding of ligands to their receptors, gradients of electrochemical potential created by ion pumps, Ca2+ mobiliza- tion, and phosphorylation and dephosphorylation.
Variation in molecular con- figuration through molecular binding is in itself sufficient to trigger ion pumps and activate kinases and phosphatases. This is one aspect of the mechanical role of the extracellular matrix dealt with herein: the induction of molecular and supramolecular conformational modifications through interactions with the cell membrane, which promote the transduction and centripetal progression of signals.

Contents:

Topological Constraints Carry Signaling from the Cell Matrix to the Genome.- 1 Variation in Cell Adhesion During Proliferation of Normal Cells.- 1.1 Coupling Between Changes in Cell Adhesion and Proliferation of Normal Cells.- 2 Coupling Between Changes in Cell Adhesion and Proliferation of Transformed Cells.- 3 Mechanisms of Cell Adhesion-Mediated Changes in the Cell Phenotype.- 3.1 Modulation of Cell Proliferation.- 3.2 Modulation of Malignancy.- 3.3 Modulation of Cell Differentiation.- 4 Conclusions.- References.- The Transmission of Contractility Through Cell Adhesion.- 1 Introduction.- 2 Generation of Contractility.- 2.1 Stress Fibers.- 2.2 Formation of Stress Fibers and Focal Adhesions.- 3 Molecular Mechanism of Force Transmission.- 3.1 Focal Adhesions.- 3.2 Mechanism of Force Transmission.- 3.3 Molecules Mediating Force Transmission.- 4 Regulation of Contractility Transmission.- 4.1 Regulation of Contractile Force.- 4.1.1 The Regulatory Mechanism of RhoA.- 4.1.2 Involvement of Microtubules.- 4.2 Regulation of Stability of Focal Adhesions.- 5 Interaction Between Contraction Force and ECM.- 6 Myofibroblasts and Wound Healing.- 7 Muscle.- 7.1 Myotendinous Junctions.- 7.2 Costameres.- 7.2.1 Contraction Force Transmission at Costameres.- 7.2.2 Potential Involvement of Dystrophin.- 7.2.3 Significance of Costameres in Heart Function.- 8 Conclusion.- References.- Role of Focal Adhesion Kinase in Signaling by the Extracellular Matrix.- 1 Introduction.- 2 FAK Activation by Integrin.- 2.1 FAK Interaction with Integrin.- 2.2 FAK Interaction with Cytoskeletal Proteins Talin, Paxillin, and Tensin.- 3 FAK Downstream Pathways.- 3.1 FAK Interaction with Src.- 3.2 FAK Interaction with PI 3-Kinase.- 3.3 FAK Interaction with p130cas.- 4 Biological Functions of FAK in Signaling by ECM.- 4.1 Cell Adhesion and Spreading.- 4.2 Cell Migration.- 4.3 Cell Survival and Apoptosis.- 4.4 Cell Cycle Progression and Proliferation.- References.- Interaction Between Cells and Extracellular Matrix: Signaling by Integrins and the Elastin-Laminin Receptor.- 1 Introduction.- 2 Cell-Matrix Interactions Mediated by Integrins.- 2.1 Signaling by Integrins.- 2.2 Evolution of Integrin Signaling with Aging.- 3 Cell-Matrix Interactions Mediated by the Elastin-Laminin Receptor.- 3.1 Signaling by the Elastin-Laminin Receptor.- 3.2 Effect of Age on the Elastin-Laminin Receptor.- 3.3 Experiments on Lymphocytes.- 4 Discussion and Conclusions.- References.- Regulation of Gene Expression by Changes in Cell Adhesion.- 1 Introduction.- 2 Regulation of Cell Proliferation by Cell Adhesion.- 2.1 Regulation of the G1 Phase.- 2.2 Molecular Basis for Regulation of the G1/S Transition.- 2.3 Regulation of Cycling A Gene Expression.- 3 Regulation of Cell Differentiation by Cell Adhesion.- 3.1 Differentiation of Hepatocytes and Regulation of Albumin Gene Expression.- 3.2 Differentiation of Mammary Epithelial Cells and Regulation of ss-Casein Gene Expression.- 4 Conclusion.- References.- Expression of Liver Specific-Genes in Hepatocytes Cultured in Collagen Gel Matr.- 1 Introduction.- 2 Culture of Hepatocytes in Collagen Gel.- 3 Hepatic Specific Functions of Hepatocytes in Collagen Cultures.- 4 Biotransformation Capability: Basal and Induced Levels of Drug-Metabolizing Enzymes.- 5 Expression of Hepatic Transcription Factors.- 6 Concluding Remarks.- References.- Collagen Type I: A Substrate and a Signal for Invasion.- 1 Introduction.- 2 Invasion into Matrices.- 2.1 The Structure of Collagen Type I.- 2.2 Technical Aspects: Different Collagen Type I Invasion Assays.- 2.3 Substrate-Dependent Differences in Invasion.- 3 Effects of Collagen on the Invasive Behavior of Cells.- 3.1 Collagen Conformation.- 3.2 Organization of the Invade/Collagen Microecosystem.- 3.3 Invasion of Cells Without External Stimuli Other Than Collagen Type I.- 3.4 Invasion, Angiogenesis, and Morphogenesis Assisted by Helper Cells.- 3.5 Invasion Stimulated by Extrinsic Factors.- 4 A Scenario for the Molecular Cross Talk Between Collagen and Cell.- 5 Conclusion.- References.