CiteULike: lechristophe's cell_mechanics

Do-it-yourself guide: how to use the modern single-molecule toolkit

Nils Walter — 2008-05-29T22:45:42-00:00

Nat Meth, Vol. 5, No. 6. (June 2008), pp. 475-489.

Single-molecule microscopy has evolved into the ultimate-sensitivity toolkit to study systems from small molecules to living cells, with the prospect of revolutionizing the modern biosciences. Here we survey the current state of the art in single-molecule tools including fluorescence spectroscopy, tethered particle microscopy, optical and magnetic tweezers, and atomic force microscopy. We also provide guidelines for choosing the right approach from the available single-molecule toolkit for applications as diverse as structural biology, enzymology, nanotechnology and systems biology.

Mechanism of shape determination in motile cells

Kinneret Keren — 2008-05-21T21:03:05-00:00

Nature, Vol. 453, No. 7194. (22 May 2008), pp. 475-480.

The shape of motile cells is determined by many dynamic processes spanning several orders of magnitude in space and time, from local polymerization of actin monomers at subsecond timescales to global, cell-scale geometry that may persist for hours. Understanding the mechanism of shape determination in cells has proved to be extremely challenging due to the numerous components involved and the complexity of their interactions. Here we harness the natural phenotypic variability in a large population of motile epithelial keratocytes from fish (Hypsophrys nicaraguensis) to reveal mechanisms of shape determination. We find that the cells inhabit a low-dimensional, highly correlated spectrum of possible functional states. We further show that a model of actin network treadmilling in an inextensible membrane bag can quantitatively recapitulate this spectrum and predict both cell shape and speed. Our model provides a simple biochemical and biophysical basis for the observed morphology and behaviour of motile cells.

RPTPalpha is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons.

A Kostic — 2008-01-03T12:49:58-00:00

J Cell Sci, Vol. 120, No. Pt 21. (1 November 2007), pp. 3895-3904.

Receptor-like protein tyrosine phosphatase alpha (RPTPalpha)-knockout mice have severe hippocampal abnormalities similar to knockouts of the Src family kinase Fyn. These enzymes are linked to the matrix-rigidity response in fibroblasts, but their function in neurons is unknown. The matrix-rigidity response of fibroblasts appears to differ from that of neuronal growth cones but it is unknown whether the rigidity detection mechanism or response pathway is altered. Here, we report that RPTPalpha is required for rigidity-dependent reinforcement of fibronectin (FN)-cytoskeleton bonds and the rigidity response in hippocampal neuron growth cones, like in fibroblasts. In control neurons, rigid FN surfaces inhibit neurite extension and neuron differentiation relative to soft surfaces. In RPTPalpha(-/-) neurons, no inhibition of extension and differentiation is found on both rigid and soft surfaces. The RPTPalpha-dependent rigidity response in neurons is FN-specific, and requires clustering of alpha(v)beta(6) integrin at the leading edge of the growth cones. Further, RPTPalpha is necessary for the rigidity-dependent concentration of Fyn and p130Cas phosphorylation at the leading edge of the growth cone, like it is in fibroblasts. Although neurons respond to rigid FN surfaces in the opposite way to fibroblasts, we suggest that the mechanism of detecting FN rigidity is similar and involves rigidity-dependent RPTPalpha recruitment of Fyn.

Comparison of quantitative methods for cell-shape analysis

Z Pincus — 2007-09-10T12:51:01-00:00

Journal of Microscopy, Vol. 227, No. 2. (2007), pp. 140-156.

Summary Morphology is an important large-scale manifestation of the global organizational and physiological state of cells, and is commonly used as a qualitative or quantitative measure of the outcome of various assays. Here we evaluate several different basic representations of cell shape - binary masks, distance maps and polygonal outlines - and different subsequent encodings of those representations - Fourier and Zernike decompositions, and the principal and independent components analyses - to determine which are best at capturing biologically important shape variation. We find that principal components analysis of two-dimensional shapes represented as outlines provide measures of morphology which are quantitative, biologically meaningful, human interpretable and work well across a range of cell types and parameter settings.

Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis

Thomas Lecuit — 2007-07-23T11:30:08-00:00

Nature Reviews Molecular Cell Biology, Vol. 8, No. 8., pp. 633-644.

Embryonic morphogenesis requires the execution of complex mechanisms that regulate the local behaviour of groups of cells. The orchestration of such mechanisms has been mainly deciphered through the identification of conserved families of signalling pathways that spatially and temporally control cell behaviour. However, how this information is processed to control cell shape and cell dynamics is an open area of investigation. The framework that emerges from diverse disciplines such as cell biology, physics and developmental biology points to adhesion and cortical actin networks as regulators of cell surface mechanics. In this context, a range of developmental phenomena can be explained by the regulation of cell surface tension.