Emergent patterns of growth controlled by multicellular form and mechanics.

By C. Nelson, R. P. Jean, John L. Tan, Wendy F. Liu, Nathan J. Sniadecki, A. Spector, Christopher S. Chen. Proceedings of the National Academy of Sciences of the United States of America, 2005

887 citations recorded by the source corpus.

Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using micro-fabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth.

Subfields: Biomedical Engineering, Cell Biology, Mechanical Engineering

View Paper: https://www.semanticscholar.org/paper/f055ce6e75d65e026da6bc9b650bdaf8a41e1c70

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Citations in the corpus

Physics of adherent cells (2013, background): “For example, it has been shown that the proliferation pattern in cell monolayers on patterned substrates correlates with the stress distribution in the thin contractile layers (Nelson et al., 2005).”
Surface engineering approaches to micropattern surfaces for cell-based assays. (2006, background): “Mechanical compliance of cell-adhering substrates can also substantially affect the cellular response and development [11].”
Balancing forces: architectural control of mechanotransduction (2011, positive): “Analogously to the cellular effects of morphogen gradients, changing tissue geometry alters tension gradients, sites of mechanotransduction and the location of the proliferating, migrating and differentiating cells within a tissu”
Mechanotransduction in development: a growing role for contractility (2009, result): “Our laboratory has reported experimental evidence in support of these models, showing that regions of high tensional stress in epithelial monolayers correlate with increased proliferation in vitro”
Intrinsic extracellular matrix properties regulate stem cell differentiation. (2010, background): “Intriguingly, micropatterns that induce cell curvature on surfaces (McBeath et al., 2004; Nelson et al., 2005; Ruiz and Chen, 2008) as well as micropores of varying size within a scaffold (O’Brien et al.”
Mechanical control of tissue and organ development (2010, background): “The application of bioengineering approaches to cell and developmental control have revealed that cytoskeletal tensiondependent changes in cell shape and variations in ECM compliance also alter the direction in which cells move and grow, which are crucial behaviors that drive tissue patterning durin”
A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. (2013, positive): “Although the molecular nature of these informational systems is uncertain, an intriguing model is that the architectural form of the tissue—its shape and three-dimensional geometry—serves as template to initiate and self-sustain asymmetric patterns of cell proliferation (Nelson and Bissell, 2006; Ne”
Mechanical compression drives cancer cells toward invasive phenotype (2011, background): “A shift in stress balance due to interactions with other cells (32, 36, 42) or cell distortion as a cell actively adapts to its local matrix environment (7, 43) can initiate cytoskeletal rearrangement, proliferation, and morphogenesis (32, 33).”
Cellular mechanotransduction: putting all the pieces together again (2006, background): “Analysis of groups of cells cultured on microfabricated adhesive islands confirm that the physical form of a tissue can feed back to control cell growth patterns as a result of local variations of internal stresses that are distributed through the cytoskeleton and resisted by cell-cell and cell-ECM ”
A model for the contractility of the cytoskeleton including the effects of stress-fibre formation and dissociation (2007, background): “When included, cell contractility has been modelled by simply prescribing a thermal strain to either a cell regarded as (i) an isotropic elastic continuum (Nelson et al. 2005) or (ii) a discrete set of elastic filaments (Mohrdieck et al.”
Engineering microscale topographies to control the cell–substrate interface (2012, background): “(d) An anisotropic ring-shaped multicellular tissue constructed on micropillars to study the effect of mechanical forces on proliferation in tissues [174].”
Mechanics, malignancy, and metastasis: The force journey of a tumor cell (2009, methodology): “These include methods for measuring mean rheological properties of whole cells, such as optical stretching [57–60], micropipette aspiration [61–65], traction force microscopy (TFM) [66–69], atomic force microscopy (AFM) [70–73], and magnetic twisting microrheometry [10, 74–77]; and microscale mechan”