Micromanipulation of the Extracellular Matrix

Objectives: Cells are inherently sensitive to local mesoscale and microscale patterns of chemistry and topography. Recent research has investigated how surface mechanics might dictate cell behavior, affecting both cell function and differentiation. This study professes that alterations of the underlying matrix can dictate cell behavior and function. Through micro-orienting the substrate and micro-patterning protein, we were able to engineer a structural and biological backbone to regulate cellular behavior.

Methods: The techniques involved in this study to control cell behavior include the micro-orienting of the ECM, electrospinning a 3D fibrous PMMA scaffold with the optimum diameter and orientation, micro-patterning of fibronectin(Fn) for cellular attachment, applying magnetic/electric fields to fibronectin, creating a novel suicide circuit for tumor targeting bacteria, and altering the stiffness of the surface to initiate cellular differentiation.

Results: Furthermore, cancer was studied and regulated at the single cell level through the alteration of the ECM mechanics. In addition, we determined that by manipulating the numerous mechanical forces acting upon the cells, the genetic and morphological changes can lead to the activation of the necessary genes to synthesize the ECM components for differentiation.

Conclusions: The use of microscale structuring to restore tissue architecture and dictate cell behavior has several important implications for tissue engineering, cancer treatment, and stem cell differentiation.