Background: Platelets are sensitive to their local mechanical environment created by flow, substrate stiffness, and others.

Aims: Quantify and predict the dynamic force response from a platelet based on substrate stiffness.

Methods: Isolated platelets were allowed to spread on a fibrinogen substrates of varied stiffness (polyacrylamide gel at 4.47±1.19 and 8.73±0.79 kPa). Spreading rates, contractile forces, and total spread area, were quantified. Force production was quantified by lacing polyacrylamide with 40 nm Fluorosphere fluorescent beads. To identify processes involved in force production and platelet spreading, we applied a computational stochastic model based on the buildup of force through myosin IIa. The model was trained by applying inhibitors and through a series of additional experiments.

Results: The final platelet spread area increased with substrate stiffness, as predicted by the stochastic model, Fig. 1, with a similar trend seen for force production. The largest forces were found around the outer edge of the spreading platelet, reaching 20 nN for our stiffest substrate of 8.73 kPa, but with various subpopulations, i.e. oscillatory vs sustained force production. Substrate stiffness-dependent force production and subpopulations were predicted by the stochastic model, based on the defined myosin IIA content in the platelet.

Conclusions: The force response from platelets demonstrates multiple subpopulations, in agreement with Hanke et al. These subpopulations can be predicted through models based on the variability of myosin IIA content in a platelet. This work builds upon earlier work from Qui et al. who initially demonstrate the sensitivity of platelets to substrate stiffness. This work is a first step in identifying unexplained bleeding or prothrombotic platelet phenotypes. It may also be leveraged in blood-contacting medical device design.

[Fig. 1: Platelet spread area relative to stiffness. Line: stochastic model. Markers: experimental measurements.]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-force-producing-subpopulations-predicted-by-a-stochastic-model/