Flow and Deformation of Cancer tumours near Yielding

Descripción del proyecto

Fuerzas mecánicas que crean células cancerosas metastásicas

Las células metastáticas se disocian de un tumor primario para formar tumores secundarios que suelen llegar a ser más agresivos y fatales. El proyecto FanCy, financiado con fondos europeos, propone un método multidisciplinario que combina ingeniería, química, biofísica y biología celular para identificar las vías mecanicistas de la metástasis. El objetivo de esa propuesta es comprender cuándo, cómo y por qué las células metastásicas se separan de un tumor. Las células de los tejidos están muy densamente compactadas, de forma que quedan retenidas en su lugar, un estado que se denomina «aglomerado». Las células aglomeradas pueden fluidificarse localmente y fluir cuando se las empuja o se deforman. Grandes fuerzas pueden llevar todo el tejido a un estado parecido a un fluido, que se denomina fluencia o «yielding». El proyecto tiene como objetivo responder a preguntas cruciales: ¿cómo se genera la «fluencia» en los tejidos? Y, ¿qué mecanismos biofísicos la provocan ?

Objetivo

The aim of this proposal is to understand when, how and why metastatic tumour cells detach from a tumour.

Often, primary tumours do not kill patients, but secondary tumours do. These so-called metastatic tumour cells disassociate from a primary tumour and, ultimately, prove fatal. Currently, we do not understand the fundamentals of the biophysical pathways and mechanisms of the metastasis of cancer, hampering medical intervention. I propose a multidisciplinary approach, combining engineering, chemistry, biophysics and cell biology to identify the mechanical pathways for the creation of metastatic cancer cells.

Biological cells in tissue are very densely packed, which locks them in place relative to their neighbours, a state referred to as jammed. The collective system of cells can become fluidised locally and flow when pushed or deformed. Even greater forces can make the entire tissue fluid-like, referred to as yielding. The crucial open questions are: how does tissue yield, and what universal physics underlies yielding?

I will develop a novel fundamental and predictive description of yielding in jammed living tissue to show:
1. How and when jammed living cells are driven to fluid-like state.
2. How confinement tunes the migration mode of cancer cells.
3. How yielding is related to the structural evolution of detached cells.
4. How critical scaling controls deformation and flow of living cells near yielding.

I will demonstrate that the distance to yielding governs the mechanical response in collective cell motion inside a tumour, and that exploiting critical scaling allows predicting the dynamics of cell detachment near yielding. The outcomes will significantly aid the treatment of cancer in the near future by bridging the gap between chemical and mechanical pathways of cancer metastasis. I have the required multidisciplinary track record. Moreover, preliminary experiments show highly promising results.