Manipulating Cell Migration and Proliferation with a Light‐Activated Polypeptide

Abstract

Remote control of cells: A polypeptide has been made that stimulates proliferation and migration of cells upon photochemical activation. This light-activated polypeptide enables spatially defined control of cell populations at the scale of tissue organization; this is accomplished without physically contacting the cells or modifying their substrate. Polypeptide growth and differentiation factors modulate a wide variety of cell behaviors and can be used to manipulate cells in vitro for tissue engineering and basic studies of cell biology. To emulate in vitro the spatial aspect of growth factor function, new methods are needed to generate defined spatial gradients of activity. Polypeptide factors that are engineered to be activated with light provide a method for creating concentration gradients with the fine precision in space and time with which light can be directed. As a first test of this approach, we have chemically synthesized a polypeptide with the sequence of epidermal growth factor in which a critical glutamate is "caged" with a photoremovable group. Photolysis of this polypeptide afforded maximal mitogenic and chemokinetic activity at concentrations at which the caged factor was inactive. Spatially resolved photolysis of the factor resulted in spatial patterning of fibroblasts. This system will be useful for ex vivo tissue engineering and for investigating the interactions of cells with their matrix and the role of chemical gradients in biological pattern formation.