Cell migration results from forces generated by assembly, contraction, and adhesion
of the cytoskeleton. To address how these forces integrate in space and time, novel
assays are required that allow spatial separation of the different force categories.
We used micro-contact printing of fibronectin on glass substrates to study the effect
of adhesion patterns on fish epidermal keratocytes locomotion. Cells migrated at similar
speeds on homogeneously adhesive substrates and on patterns with 5 pm-wide adhesive
stripes interleaved by non-adhesive stripes with a width varied between 5 and 13 pm.
The leading edge protruded on adhesive stripes and lagged behind on non-adhesive stripes.
On patterns with non-adhesive stripes wider than 13 pm cells halted, although the
lamellipodium did not collapse. High correlation was found between the widths of protruding
and lagging edge segments and the widths of the underlying stripes. We explain our
data by the force balances between actin polymerization, contraction and adhesion
on fibronectin stripes; and between actin polymerization, contraction and lamellipodium-internal
elastic tension on non-adhesive stripes. We tested our model further by blocking lamellipodium
actin network contraction and polymerization. In both experiments we observed that
cells eventually lost their ability to move. However, the two perturbations induced
distinct morphological responses. The data suggested that forces powering forward
motion of keratocytes are largely associated with network assembly whereas contraction
maintains cell polarity. This study establishes spatially selective adhesion substrates
and cell morphological readouts as a means to elucidate the mechanical balance between
substrate adhesion and cytoskeleton-internal tension in cell migration.
