Medical Engineering & Physics 27 (2005) 763–772 Physical determinants of cell organization in soft media Ulrich S. Schwarz a,b,∗ , Ilka B. Bischofs a,b a MaxPlanckInstituteofColloidsandInterfaces,14424Potsdam,Germany b UniversityofHeidelberg,IWR/BIOMS,INF368,69120Heidelberg,Germany Received 7 February 2005; accepted 11 April 2005 Abstract Cell adhesion is an integral part of many physiological processes in tissues, including development, tissue maintenance, angiogenesis, and wound healing. Recent advances in materials science (including microcontact printing, soft lithography, microfluidics, and nanotechnology) have led to strongly improved control of extracellular ligand distribution and of the properties of the micromechanical environment. As a result, the investigation of cellular response to the physical properties of adhesive surfaces has become a very active area of research. Sophisticated use of elastic substrates has revealed that cell organization in soft media is determined by active mechanosensing at cell-matrix adhesions. In order to determine the underlying mechanisms, quantification and biophysical modelling are essential. In tissue engineering, theory might help to design new environments for cells. © 2005 IPEM. Published by Elsevier Ltd. All rights reserved. Keywords: Cell-matrix adhesion; Focal adhesions; Cytoskeleton; Mechanotransduction 1. Introduction The human body consists of around 10 13 cells, which can be classified into more than 200 different cell types. Like all complex organisms, our body is organized in a hierarchical way: cells together with extracellular matrix (ECM) form tissues, and tissues form organs. What distinguishes a clot of cells and matrix from a tissue is the well-defined organization of cells and ECM, which is closely associated with tissue function. Within a tissue, cells adopt well- defined gene expression patterns, morphologies, positions and orientations. Loss of cell organisation leads to tissue malfunction and disease. Tissue organisation affects many different physiological processes, including development, tissue maintenance, angiogenesis, and wound healing. The key question in understanding tissue organization is how cells communicate with each other and their environment to build-up organized structures. The research in cell and tissue organization principles has a long history and today we know that cells integrate information received through ∗ Corresponding author. E-mailaddress: Ulrich.Schwarz@iwr.uni-heidelberg.de (U.S. Schwarz). many different channels. Fig. 1 shows an overview of known factors influencing cell and tissue organization. The main mean of communication is release and capture of biochemical molecules. In cell migration, this leads to chemotaxis, that is directed movement along a chemical gradient [1]. Many different cell types employ chemotaxis, for example neutrophils homing in for pathogens and growth cones during neural development. In the context of tissue organization, chemotaxis is involved for example in morphogenesis, angiogenesis, and wound healing. By using the lock-and-key principle of ligand-receptor binding, cells can exchange very specific information. When cells are suspended in solution, they can capture signalling molecules which are distributed according to the physical laws of diffusion and reaction. In contrast, when cells adhere to an extracellular structure, in addition they can bind biochemical ligands which are attached to external surfaces, for example to the plasma membrane of other cells or the proteins and sugars of the ECM. Therefore, in cell adhesion, the bio- chemical information is supplemented by several additional degrees of information, including spatial distributions of ligands which are not determined by diffusion, and the topo- graphical and mechanical properties of the structure the cell attaches to. 1350-4533/$ – see front matter © 2005 IPEM. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.medengphy.2005.04.007