Overview Cell Structures Cell Migration Cell Division  

Requirement of Focal Adhesion Kinase for Sensing Mechanical Signals

Wang et al. Proc. Natl. Acad. Sci. USA 98:11295-11300 (2001)

Focal adhesion kinase (FAK), a tyrosine kinase located at focal adhesions, is believed to play an important role in transducing adhesion signals applied to the external domain of integrin into chemical cascades inside the cell.  The purpose of this study is to test the hypothesis that FAK is required for cellular responses to mechanical signals detected at integrins, such as the sensing of forces and stiffness.  We use a fibroblast cell line engineered to suppress the expression of FAK in the presence of tetracyclin.  This allows us to compare cells with and without FAK by culturing cells in the absence or presence of tetracyclin.


Migration of Control Fibroblasts Expressing FAK

Control fibroblasts migrate on glass surfaces in a manner commonly described as persistent random walk, where a cell migrates along a direction for a period that defines the persistence then switches the direction randomly.  Duration 180 min.


Migration of FAK-Null Fibroblasts

FAK-null fibroblasts migrate in a similar but partially impaired manner.  Quantitative analysis of the trajectories indicate reduced persistence and speed.  Duration 180 min.


Responses to Pushing Forces

To test the responses to forces applied through the substrate, fibroblasts are cultured on elastic polyacrylamide surfaces.  A glass need is then used to push the substrate against the cell.  Control fibroblast responds by turning away from the needle (right).  FAK-null fibroblast is unable to respond to such pushing forces (left).  Duration 27 min.


Durotaxis of Control Fibroblasts Expressing FAK

Durotaxis is the ability of adherent cells to migrate away from soft surfaces in favor of stiff surfaces .  This video shows a control fibroblasts moving initially from a stiff surface (top half) onto a soft surface (lower half, labeled with fluorescent particles),  The cell then turns around to return to the stiff surface.  Duration 240 min.


Inhibition of Durotaxis of FAK-Null Fibroblasts

This video shows a FAK-null fibroblast moving from a stiff surface (left hand half) onto a soft surface (right hand half, labeled with fluorescent particles).  The cell then continues with the migration deep into the soft region.  Duration 240 min.