University of Louisville

Poster Title

TGF-β1 Enhances Confined Migration Through Cell Softening in Mesenchymal Glioblastoma

Grade Level at Time of Presentation

Junior

Major

Bioengineering

2nd Grade Level at Time of Presentation

Junior

2nd Student Major

Bioengineering

Institution

University of Louisville

KY House District #

33;59

KY Senate District #

36;26

Department

Department of Bioengineering

Abstract

Glioblastoma (GBM) is an incurable and highly aggressive cancer with a dismal prognosis. The evolution of GBM is coupled with a proneural-to-mesenchymal transition (PMT) that exacerbates disease in part through heightened cell invasiveness and spread. Notably, the rapid infiltration of mesenchymal GBM cells occurs despite there being tight physical barriers in the dense brain parenchyma. Recent work has suggested that efficient confined migration is key to navigating these physical constraints; however, the mechanisms that drive robust confined migration remain unclear. Here, we explore this question through a biophysical lens to investigate the relationship between mechanical alterations associated with GBM mesenchymal transformation and functional confined migration. We hypothesize that TGF-β1 promotes efficient confined migration by activating mesenchymal pathways that mechanically soften the cell. U87-MG GBM cells were treated with TGF-β1 and assessed for changes in protein expression, mechanical rigidity, and confined migration. The data suggest that TGF-β1 induced mesenchymal transitions are associated with changes in cell structural proteins. We further reveal that these protein level changes soften the cell, leading to a functional increase in migration potential under tight confinement. This study presents novel insights into the mechanical changes that occur during mesenchymal transitions in GBM and highlights new biophysical perspectives to consider in our treatment of GBM.

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TGF-β1 Enhances Confined Migration Through Cell Softening in Mesenchymal Glioblastoma

Glioblastoma (GBM) is an incurable and highly aggressive cancer with a dismal prognosis. The evolution of GBM is coupled with a proneural-to-mesenchymal transition (PMT) that exacerbates disease in part through heightened cell invasiveness and spread. Notably, the rapid infiltration of mesenchymal GBM cells occurs despite there being tight physical barriers in the dense brain parenchyma. Recent work has suggested that efficient confined migration is key to navigating these physical constraints; however, the mechanisms that drive robust confined migration remain unclear. Here, we explore this question through a biophysical lens to investigate the relationship between mechanical alterations associated with GBM mesenchymal transformation and functional confined migration. We hypothesize that TGF-β1 promotes efficient confined migration by activating mesenchymal pathways that mechanically soften the cell. U87-MG GBM cells were treated with TGF-β1 and assessed for changes in protein expression, mechanical rigidity, and confined migration. The data suggest that TGF-β1 induced mesenchymal transitions are associated with changes in cell structural proteins. We further reveal that these protein level changes soften the cell, leading to a functional increase in migration potential under tight confinement. This study presents novel insights into the mechanical changes that occur during mesenchymal transitions in GBM and highlights new biophysical perspectives to consider in our treatment of GBM.