Engineering Cell Form and Function with Nanometric Surfaces

Mathis Riehle, David Gilbert, Chris Wilkinson and Stephen Yarwood,

A collaboration between the Centre for Cell Engineering and the Bioinformatics Research Centre

Funded under the Royal Society Wolfson Foundation Laboratory Refurbishment Scheme

Bioinformatics Lab
Cell Engineering Lab

Nanometric features are fabricated on the surface of polymers, which are either random or ordered, and which can either be of chemical or of topographic nature. The nanofeatured surfaces are used to investigate the interaction of cells with this nano-designed interface. The cellular reaction is studied using classical and modern cell biological methods including gene-microarrays. The planned integration with the bioinformatics group will allow the further discovery of the genetic components regulating cell shape and function. This research is undertaken with the explicit aim to exploit any useful reaction to foster designed cell surface interactions at e.g. implant or tissue engineering scaffolds.

The proposed research will combine cutting edge nanotechnology to engineer cell surface interactions and cell biological investigations together with advanced bioinformatic tools to analyse and understand the reaction of the cells to a changed tactile environment on a molecular and system level. There is ample evidence that human cells in contact with materials surfaces react to the mechanical, chemical and topographic surface properties and adapt in accordance with their internal genetic and metabolic status. Furthermore the natural environment of cells contains chemical and topographic features covering length scales down to nanometer and cells react to artificial structures of that size. If we were able to understand the reaction of cells to a tactile environment intentionally modified by nanometric patterns, the interaction of cells with implant surfaces and tissue-engineering scaffolds could be improved on a rational basis. There is some data available to illustrate the changes in cell physiology, protein localisation and gene expression of cells in contact with designed nanometric surfaces. The problem lies in identifying relevant changes, which will influence cell behaviour over longer periods of time and finding a logical explanation for the changes as well as a rationale to improve cell-biomaterial interaction. We will be using bioinformatic approaches to allow the systematic analysis of the expression activity and to investigate the protein networks formed in the focal adhesions, which constitute the cell-surface link, to identify interesting targets for further investigations. We currently have access to electron beam lithography to generate a variety of surface patterns, and to electroplating facilities to create nickel shims, which then can be used in the new facility to emboss polymer surfaces. Micro- and nanocontact stamps made in a similar way will be used to fabricate chemical patterns with sub-micron resolution.