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Geometric Control of Cell Life and DeathChristopher S. Chen, Milan Mrksich, Sui Huang, George M. Whitesides, and Donald E. IngberScience, 1997
Michael Batista1,2
Brian Carvalho1,3
Department of Biological Engineering, MITDepartment of Material Science Engineering, MITDepartment of Physics, MIT
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The Capabilities of Cancer
Hanahan and Weinberg, Cell, Vol. 100, 57-70, 2000Siemann DW., Vascular targeting agents. Horizons in Cancer Therapeutics: From Beach to Bedside. 2002;3(2):4-15
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Apoptosis: ECM Adhesion vs. Cell Geometry
Integrins: Transduce mechanical stimuli into/out of the cell
Proliferation
Apoptosis
Differentiation
Cell Shape: Implicated in triggering apoptosis independent of ECM
Apoptosis
Survival
4.5µm
100µm
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Cell Spreading and ECM Exposure Inhibits Apoptosis
Nuclei
Differences in cell curvature, bead engulfment, and ECM contact area confound the trend in B
Restricting cells to flat pads eliminates these complications
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Apoptosis: Effect of Cell Surface Area
Holding ECM contact area constant does not change survival effect of increasing cell surface area.
Pad Size: Pad Spacing
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Apoptosis: Effect of Integrin Binding
β-1 Ligand
β-3 Ligand
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Conclusions
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Current Work: Mechanotransduction
Apoptosis Differentiation Anti-Apoptosis
Mammary EpithelialLIF JAK/STAT3
MSCsRhoA ROCK
OsteocytesSrc ERK
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Questions