@entity1 neutrophils are mediators of innate immunity and undergo dramatic shape changes at all stages of their functional life cycle. In this work, we quantified the forces associated with a neutrophil's morphological transition from a nonadherent, quiescent sphere to its adherent and spread state. We did this by tracking, with high spatial and temporal resolution, the cell's mechanical behavior during spreading on microfabricated post-array detectors printed with the extracellular matrix protein  fibronectin. Two dominant mechanical regimes were observed: transient protrusion and steady-state contraction. During spreading, a wave of protrusive force (75    8 pN/post) propagates radially outward from the cell center at a speed of 206    28  nm/s. Once completed, the cells enter a sustained contractile state. Although post engagement during contraction was continuously varying, posts within the core of the contact zone were less contractile (-20    10 pN/post) than those residing at the geometric perimeter (-106    10 pN/post). The magnitude of the protrusive force was found to be unchanged in response to cytoskeletal inhibitors of lamellipodium formation and myosin II-mediated contractility. However, @entity2389 , known to reduce cortical @entity2701 in neutrophils, slowed spreading velocity (61    37  nm/s) without significantly reducing protrusive force. Relaxation of the actin cortical shell was a prerequisite for spreading on post arrays as demonstrated by stiffening in response to @entity13298 and the abrogation of spreading. ROCK and myosin II inhibition reduced long-term contractility. Function blocking antibody studies revealed haptokinetic spreading was induced by b2 integrin ligation. Neutrophils were found to moderately invaginate the post arrays to a depth of    1  m as measured from spinning disk confocal microscopy. Our work suggests a competition of adhesion energy, cortical @entity2701 , and the relaxation of cortical @entity2701 is at play at the onset of neutrophil spreading.

Protrusive and Contractile Forces of Spreading XXXX Neutrophils.

@entity1 :: ('9606', 'Species') :: ['Human'] @entity13298 :: ('MESH:C057531', 'Chemical') :: ['jasplakinolide'] @entity2389 :: ('MESH:D003571', 'Chemical') :: ['cytochalasin B'] @entity2701 :: ('MESH:D018781', 'Disease') :: ['tension']
@entity1 :: (9606,Species) :: ['Human']
