Focal adhesions are large protein complexes organized at the basal surface of 
cells, which physically connect the extracellular matrix to the cytoskeleton and 
have long been speculated to mediate cell migration. However, whether clustering 
of these molecular components into focal adhesions is actually required for 
these proteins to regulate cell motility is unclear. Here we use quantitative 
microscopy to characterize descriptors of focal adhesion and cell motility for 
mouse embryonic fibroblasts and human fibrosarcoma cells, across a wide range of 
matrix compliance and following genetic manipulations of focal adhesion proteins 
(vinculin, talin, zyxin, FAK, and paxilin). This analysis reveals a tight, 
biphasic gaussian relationship between mean size of focal adhesions (not their 
number, surface density, or shape) and cell speed. The predictive power of this 
relationship is comprehensively validated by disrupting nonfocal adhesion 
proteins (α-actinin, F-actin, and myosin II) and subcellular organelles 
(mitochondria, nuclear DNA, etc.) not known to affect either focal adhesions or 
cell migration. This study suggests that the mean size of focal adhesions 
robustly and precisely predicts cell speed independently of focal adhesion 
surface density and molecular composition.