Faculty Opinions recommendation of FAK promotes recruitment of talin to nascent adhesions to control cell motility.

Author(s):  
Donna Webb
Keyword(s):  
2021 ◽  
Author(s):  
Subhaya Bose ◽  
Kinjal Dasbiswas ◽  
Arvind Gopinath

AbstractThe mechanical micro–environment of cells and tissues influences key aspects of cell structure and function including cell motility. For proper tissue development, cells need to migrate, interact with other neighbouring cells and form contacts, each of which require the cell to exert physical forces. Cells are known to exert contractile forces on underlying soft substrates. These stresses result in substrate deformation that can affect migratory behavior of cells as well as provide an avenue for cells to sense each other and coordinate their motion. The role of substrate mechanics, particularly its stiffness, in such biological processesis therefore a subject of active investigation. Recent progress in experimental techniques have enabled key insights into pairwise mechanical interactions that control cell motility when they move on compliant soft substrates. Analysis and modeling of such systemsis however still in its nascent stages. Motivated by the role modeling is expected to play in interpreting, informing and guiding experiments, we build a biophysical model for cell migration and cell–cell interactions. Our focus is on situations highly relevant to tissue engineering and regenerative medicine –when substrate traction stresses induced by motile cells enable substrate deformation and serve as a medium of communication. Using a generalizable agent–basedmodel, we compute key metrics of cell motile behavior such as the number of cell–cell contacts over a given time, dispersion of cell trajectories, and probability of permanent cell contact, and analyze how these depend on a cell motility parameter and on substrate stiffness. Our results provide a framework towards modeling the manner in which cells may sense each other mechanically via the substrate and use this information to generate coordinated movements across much longer length scales. Our results also provide a foundation to analyze experiments on the phenomenon known as durotaxis where single cells move preferentially towards regions of high stiffness on patterned substrates.


1999 ◽  
Vol 1 (10) ◽  
pp. 1-16
Author(s):  
Geoffrey L. Smith ◽  
Christopher M. Sanderson

Viruses replicate inside host cells, where they use host biochemical and structural components to facilitate the production of new virus particles. As a consequence of co-evolution with their hosts, viruses have acquired host genes and genetic mutations that confer dominance over normal cell function. Research on virus–cell interactions has focused on the identification of mechanisms of virus dominance in order to develop therapeutic strategies for preventing productive infection. Although such research remains an essential part of molecular virology, viruses are also important genetic tools that can be used to analyse cell function. Because virus genomes contain genetic information, some of which was derived from host cells, it is possible that the analyses of virus–host interactions might lead to the identification of functionally dominant virus genes and novel eukaryotic counterparts. In this article, we have described how transforming and non-transforming viruses can control cell motility (cell migration or membrane projection), and explained how the analysis of virus cytopathic effects (CPEs) led to the identification of a novel family of cellular genes that regulate diverse aspects of cell motility.


2021 ◽  
Author(s):  
Koji Kikuchi ◽  
Yasuhisa Sakamoto ◽  
Akiyoshi Uezu ◽  
Hideyuki Yamamoto ◽  
Kei-ichiro Ishiguro ◽  
...  

Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. Herein, we show that MAP7 family protein Map7D2 facilitates MT stabilization to control cell motility and neurite outgrowth. Map7D2, was highly expressed in the brain and testis, directly bound to MTs through its N-terminal half similarly to Map7, and promoted MT stabilization in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in N1-E115 mouse glioblastoma cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the intensity of MTs without affecting stable MT markers acetylated and detyrosinated tubulin, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. The other MAP7 family protein expressed in N1-E115, Map7D1, exhibited similar subcellular localization and gene knock-down phenotypes. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated tubulin levels. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms for the control of cell motility and neurite outgrowth.


2017 ◽  
Vol 131 (3) ◽  
pp. jcs204644 ◽  
Author(s):  
Arzu Ulu ◽  
Wonkyung Oh ◽  
Yan Zuo ◽  
Jeffrey A. Frost

2021 ◽  
Author(s):  
Thomas P Prescott ◽  
Kan Zhu ◽  
Min Zhao ◽  
Ruth E Baker

ABSTRACTCell motility in response to environmental cues forms the basis of many developmental processes in multicellular organisms. One such environmental cue is an electric field (EF), which induces a form of motility known as electrotaxis. Electrotaxis has evolved in a number of cell types to guide wound healing, and has been associated with different cellular processes, suggesting that observed electrotactic behaviour is likely a combination of multiple distinct effects arising from the presence of an EF. In order to determine the different mechanisms by which observed electrotactic behaviour emerges, and thus to design EFs that can be applied to direct and control electrotaxis, researchers require accurate quantitative predictions of cellular responses to externally-applied fields. Here, we use mathematical modelling to formulate and parametrise a variety of hypothetical descriptions of how cell motility may change in response to an EF. We calibrate our model to observed data using synthetic likelihoods and Bayesian sequential learning techniques, and demonstrate that EFs impact cellular motility in three distinct ways. We also demonstrate how the model allows us to make predictions about cellular motility under different EFs. The resulting model and calibration methodology will thus form the basis for future data-driven and model-based feedback control strategies based on electric actuation.SIGNIFICANCEElectrotaxis is attracting much interest and development as a technique to control cell migration due to the precision of electric fields as actuation signals. However, precise control of electrotactic migration relies on an accurate model of how cell motility changes in response to applied electric fields. We present and calibrate a parametrised stochastic model that accurately replicates experimental single-cell data and enables the prediction of input–output behaviour while quantifying uncertainty and stochasticity. The model allows us to quantify three distinct ways in which electric fields perturb the motile behaviour of the cell. This model and the associated simulation-based calibration methodology will be central to future developments in the control of electrotaxis.


2012 ◽  
Vol 196 (3) ◽  
pp. 387-387 ◽  
Author(s):  
Christine Lawson ◽  
Ssang-Taek Lim ◽  
Sean Uryu ◽  
Xiao Lei Chen ◽  
David A. Calderwood ◽  
...  
Keyword(s):  

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