Cells continuously sense and respond to external mechanical forces through their 
cytoskeleton. Here we show that only a small subset of actin fibers, those 
forming the perinuclear actin cap that wraps around the nucleus, form in 
response to low physiological mechanical stresses in adherent fibroblasts. While 
conventional basal stress fibers form only past a threshold shear stress of 0.5 
dyn/cm(2), actin-cap fibers are formed at shear stresses 50 times lower and 
orders-of-magnitude faster than biochemical stimulation. This fast differential 
response is uniquely mediated by focal adhesion protein zyxin at low shear 
stress and actomyosin fibers of the actin cap. We identify additional roles for 
lamin A/C of the nuclear lamina and linkers of nucleus to cytoskeleton (LINC) 
molecules nesprin2giant and nesprin3, which anchor actin cap fibers to the 
nucleus. These results suggest an interconnected physical pathway for 
mechanotransduction, from the extracellular milieu to the nucleus.