  Adhering cells actively probe the mechanical properties of their environment
and use the resulting information to position and orient themselves. We show
that a large body of experimental observations can be consistently explained
from one unifying principle, namely that cells strengthen contacts and
cytoskeleton in the direction of large effective stiffness. Using linear
elasticity theory to model the extracellular environment, we calculate optimal
cell organization for several situations of interest and find excellent
agreement with experiments for fibroblasts, both on elastic substrates and in
collagen gels: cells orient in the direction of external tensile strain, they
orient parallel and normal to free and clamped surfaces, respectively, and they
interact elastically to form strings. Our method can be applied for rational
design of tissue equivalents. Moreover our results indicate that the concept of
contact guidance has to be reevaluated. We also suggest that cell-matrix
contacts are upregulated by large effective stiffness in the environment
because in this way, build-up of force is more efficient.
