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Biomedical subjects

G Forgacs

Publications and source records attributed to G Forgacs.

30 records · Page 2Linked to original sources

Wetting, percolation and morphogenesis in a model tissue system.

Artificial tissues constructed of cells or polystyrene beads suspended in a solution of type I collagen will, under appropriate conditions, protrude into regions of similar matrices lacking particles, but containing the extracellular glycoprotein fibronectin. This phenomenon has been termed "matrix-driven translocation". Conditions required for the effect include the presence of heparin-like molecules on the cell or bead surfaces, appropriate concentrations of particles and collagen, and physiological ionic strength and pH. Here we consider the idea that the driving force for the concerted movement of matrix and suspended particles is the thermodynamically spontaneous spreading or wetting behavior of two immiscible fluids bounded by common substrata. Wetting theory is shown to be capable of accounting for the behavior of this model system, but this analysis requires that the two matrix regions constitute separate phases at thermodynamic coexistence. We show that one plausible mechanism for the generation of separate phases is the formation of a percolation network of collagen fibers on a lattice of cells or beads. It is argued that the concepts of wetting and percolation apply to properties in common between the model system and living tissues, and may therefore be used to provide a physical account of aspects of tissue morphogenesis.

Cell Adhesion↗

Biological specificity and measurable physical properties of cell surface receptors and their possible role in signal transduction through the cytoskeleton.

It is proposed that the binding specificities of cell adhesion molecules are manifested in their measurable physical properties. A method specifically designed to measure the interfacial tension of cell aggregates is described. With the introduction of a statistical mechanical model, the measured values of tensions for aggregates consisting of genetically engineered cells with controlled adhesive properties are used to obtain information on the strength of individual receptor-ligand bonds. The strength of binding must depend on the receptor and its ligand and reflects the amino acid sequence of the binding proteins. Many of the cell surface receptors, being transmembrane proteins, are attached to the various macromolecular networks of the cytoskeleton; therefore, it is suggested that their ligation and ensuing conformational change may substantially affect the mechanical state of the cytoskeletal assemblies. Since these assemblies are believed to actively participate in intracellular signaling by transmitting signals from the cell membrane into the nucleus, the cell adhesion molecules may influence signaling in a predictable way through their measurable physical characteristics. In particular, varying bond strength at the cell surface may lead to differential gene regulation.

Biomechanical Phenomena↗