Signaling Through the Cell Matrix

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.

This book covers a hot subject in cell biology; i.e. how the cell environment sends messages to the cell, regulates gene expression, and modulates the cell phenotype. For a long time the extracellular matrix was believed to have only a supporting role for cell attachement. However, it became apparent that the matrix participates actively in cell metabolism. The experiments that led to this conclusion are described in this volume. Progressively, molecules have been identified that transmit this signaling at the cell-matrix interface. Their identity and mechanism of action are also illustrated in this book. Finally, it explains the role the cell-matrix relationship plays in the regulation of cell proliferation, cell differentiation, and the expression of malignancy.