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Sebastien Uzel

Email: suzel@mit.edu

Focus group: Biologocal machines, Differentiation

Department: Mechanical engineering

Hometown: Lorient, France

Undergrad: Lycee Clemenceau, Nantes; Ecole Centrale Paris, France


Research summary:

Eighty five percent of cancer related deaths are due to solid tumors, and the majority of these deaths are caused by the formation of metastases. Metastasis formation is a complex, multistage process involving modulation of cell phenotype, cell migration, and dynamic homotypic and heterotypic cell-cell interactions. Following EMT, cells migrate away from the primary tumor mass in response to an ensemble of extracellular signals, including ECM mechanical properties, paracrine signals, autocrine signals, ECM-bound ligand, and applied force. The numerous migratory stimuli act in parallel and compete to guide the direction, velocity, and persistence of cell migration.
Evaluating the importance of various stimuli requires engineered systems in which we can modulate the relative strength of each stimulus. We developed a microfluidic system in which we can modulate the chemical and mechanical microenvironment of tumor cells, and we have used this system to investigate the role of fluid flow on cell migration. We found that chemical stimuli, resulting from the redistribution of soluble ligand in a flow field, compete with mechanical stimuli, resulting from fluid shear and pressure stresses on the cell, to guide cell migration. We are using data gleaned from the microfluidic system to develop a computational model for chemotaxis and durotaxis of tumor cells through 3D matrices. This model will be employed to interpret experimental data of cell migration in response to competing stimuli and to aide in the design of engineered tissues and biological machines.

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