Join us on May 5th for our Weekly Chemistry Seminar! Guest Speaker, Dr. Ryan Petrie, will be joining us from the Department of Biology at Drexel University.

 

Abstract: Primary human fibroblasts can use at least two distinct mechanisms or modes of migration through three-dimensional (3D) matrices. In these cells, actomyosin contractility pulls the nucleus forward like a piston to increase cytoplasmic hydraulic pressure and switch cells from using low-pressure lamellipodia to high-pressure lobopodial protrusions. Though this nuclear piston mechanism of migration is triggered specifically within 3D matrices that act as a barrier to the passage of the bulky nucleus, how it is activated remains unclear. Here, we show that there is a significant increase in nuclear mechanical stress when the piston is activated, as measured by nuclear deformation and pressure. However, these physical changes are not sufficient to activate the piston mechanism. Ultimately, we found that the Ras-MAPK pathway acts as a molecular switch in response to the physical structure of the 3D extracellular matrix to activate the nuclear piston mechanism of 3D migration and prevent the formation of lamellipodial protrusions.

 

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