Integrative Tissue Dynamics Laboratory

 

 

 

Research

Cell motility and tissue dynamics

The ability of eukaryotic cells to migrate within living organisms underlies a wide range of phenomena in health and disease. When properly regulated, cell migration enables morphogenesis, host defense, and tissue healing. When regulation fails, however, cell migration mediates devastating pathologies such as cancer, vascular disease and chronic inflammation. Our research focuses in understanding the fundamental biophysical mechanisms underlying migration both at the single cell level and at the tissue level.

 

a) Epithelial sheet collectively migrating on a collagen matrix. b) Map of the traction forces exerted by the migrating cells on the matrix c) Tug-of-war model integrating local force generation into a global state of tension ( Nature Phys , 2009).

 

Cytoskeletal fragility

With every beat of the heart, inflation of the lung, or peristalsis of the gut, cell types of diverse function are subjected to substantial mechanical forces. How cells sense and respond to such forces underlies fundamental biological functions including differentiation, proliferation, polarization, locomotion, invasion, gene expression, and pattern formation. We recently identified a new class of universal cellular responses to mechanical forces we termed “cytoskeletal fluidization” (Trepat et al, Nature, 2007). The existence of this response class implies that the cytoskeleton of the living cell should no longer be regarded as a robust and stable scaffold but as a fragile one that is able to fluidize and quickly reorganize to adapt to its active mechanical environment. Our current research focuses on better understanding the functional implications of cytoskeletal fluidization and elucidating the underlying physical mechanisms.

 

Selected Publications

Trepat X, Wasserman MR, Angelini TE, Millet E, Weitz DA, Butler JP, Fredberg JJ. Physical forces during collective cell migration. Nature Phys 5, 426 (2009).

Zhou E, Trepat X, Park CY, Lenormand G, Oliver M, Mijailovich SM, Hardin C, Weitz DA, Butler JP, Fredberg JJ. Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition. PNAS 106, 10632 (2009) .

An SS, Kim J, Ahn K, Trepat X, Drake KJ, Kumar S, Ling G, Purington C, Rangasamy T, Kensler TW, Mitzner W, Fredberg JJ, Biswal S. Cell stiffness, contractile stress and the role of extracellular matrix. Biochem Biophys Res Commun 382 (4), 697 (2009).

Krishnan R, Park CY, Lin YC, Mead J, Jaspers RT, Trepat X, Lenormand G, Tambe D, Smolensky AV, Knoll AH, Butler JP, Fredberg JJ. Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness. PLoS ONE 4 (5), e5486 (2009).

Krishnan R, Trepat X, Nguyen TT, Lenormand G, Oliver M, Fredberg JJ. Airway smooth muscle and bronchospasm: Fluctuating, fluidizing, freezing. Respir Physiol Neurobiol 163 (1-3), 17 (2008).

Trepat X, Farre R. Alveolar permeability and stretch: Too far, too fast. Eur Respir J 32 (4), 826 (2008).

Trepat X, Lenormand G, Fredberg JJ. Universality in cell mechanics. Soft Matter 4, 1750 (2008).

Bursac P, Fabry B, Trepat X, Lenormand G, Butler JP, Wang N, Fredberg JJ, An SS. Cytoskeleton dynamics: Fluctuations within the network. Biochem Biophys Res Commun 355 (2), 324 (2007).

Trepat X, Deng L, An SS, Navajas D, Tschumperlin DJ, Gerthoffer WT, Butler JP, Fredberg JJ. Universal physical responses to stretch in the living cell. Nature 447 (7144), 592 (2007).

An SS, Fabry B, Trepat X, Wang N, Fredberg JJ. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness? Am J Respir Cell Mol Biol 35 (1), 55 (2006).

Deng L, Trepat X, Butler JP, Millet E, Morgan KG, Weitz DA, Fredberg JJ. Fast and slow dynamics of the cytoskeleton. Nature Mater 5 (8), 636 (2006).

Trepat X, Puig F, Gavara N, Fredberg JJ, Farre R, Navajas D. Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin. Am J Physiol Lung Cell Mol Physiol 290 (6), L1104 (2006).

Trepat X, Grabulosa M, Buscemi L, Rico F, Farre R, Navajas D. Thrombin and histamine induce stiffening of alveolar epithelial cells. J Appl Physiol 98 (4), 1567 (2005).

Rigau J, Farre R, Trepat X, Shusterman D, Navajas D. Oscillometric assessment of airway obstruction in a mechanical model of vocal cord dysfunction. J Biomech 37 (1), 37 (2004).

Trepat X, Grabulosa M, Puig F, Maksym GN, Navajas D, Farre R. Viscoelasticity of human alveolar epithelial cells subjected to stretch. Am J Physiol Lung Cell Mol Physiol 287 (5), L1025 (2004).

Alcaraz J, Buscemi L, Grabulosa M, Trepat X, Fabry B, Farre R, Navajas D. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys J 84 (3), 2071 (2003).

Trepat X, Grabulosa M, Buscemi L, Rico F, Fabry B, Fredberg JJ, Farre R. Oscillatory magnetic tweezers based on ferromagnetic beads and simple coaxial coils. Rev Sci Instrum 74 (9), 4012 (2003).

Farre R, Montserrat JM, Rigau J, Trepat X, Pinto P, Navajas D. Response of automatic continuous positive airway pressure devices to different sleep breathing patterns: A bench study. Am J Respir Crit Care Med 166 (4), 469 (2002).

 

News and Views on our work

How do cells move: Cooperative forces boost collective mobility of cells, Science Daily

Cells guided on their journey, Nature Physics

Disorderly conduct, Harvard Medical School Focus

How growing cells move together, Harvard Science Foundation

A stretch in cells, Nature

More than lip service, Nature

 

Catalan / Spanish

L'observador, Spanish National Radio

Europa premia vuit joves investigadors de Catalunya, Avui

Com actuen les forces físiques durant la migració cel·lular?, Comunicacions UB

 

Collaborators

Jeff Fredberg, Harvard University

Jim Butler, Harvard University

Benoit Ladoux, Université Paris-7

Ken Jacobson, University of North Carolina – Chapel Hill

Klaus Kroy, Universität Leipzig

Joaquim Gea, Hospital del Mar, Barcelona