During cell migration, the cell edge undergoes periodic protrusion–retraction cycles. Quantitative analyses of the forces at the cell edge that drive these cycles are provided. We show that α-actinin links local contractile units and the global actin flow forces at the cell edge and present a novel model based on these results.

Cells sense the rigidity of their environment through localized pinching, which occurs when myosin molecular motors generate contractions within actin filaments anchoring the cell to its surroundings. We present high-resolution experiments performed on these elementary contractile units in cells. Our experimental results challenge the current understanding of molecular motor force generation. Surprisingly, bipolar myosin filaments generate much larger forces per motor than measured in single molecule experiments. Further, contraction to a fixed distance, followed by relaxation at the same rate, is observed over a wide range of matrix rigidities. Lastly, step-wise displacements of the matrix contacts are apparent during both contraction and relaxation. Building upon a generic two-state model of molecular motor collections, we interpret these unexpected observations as spontaneously emerging features of a collective motor behavior. Our approach explains why, in the cellular context, collections of resilient and slow motors contract in a stepwise fashion while collections of weak and fast motors do not. We thus rationalize the specificity of motor contractions implied in rigidity sensing compared to previous in vitro observations.

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The oral effectiveness of isosorbide dinitrate (Isoket) was tested in 21 pateints with acute myocardial infarction. Patients were divided into two groups according to thier initial left-ventricular filling pressure (more or less than 20 mm Hg). In both groups there was a highly significant decrease in pulmonary artery pressure. In group I (less than 20 mm Hg) the left-ventricular filling pressure fell from 13.6 +/- 4.0 to 7.1 +/- 2.6 mm Hg, while in group II it fell from 26.9 +/- 4.6 to 19.0 +/- 3.6 mm Hg (P less than 0.001). The cardiac output fell in group I from 5.1 +/- 1.0 to 4.5 +/- 0.9 l/min, while in group II there was a significant rise from a low value (3.5 +/- 0.8 l/min) to 4.1 +/- 0.9 l/min (P less than 0.001). In both groups there was a slight but not significant fall in arterial blood pressure, while heart rate remained constant.