Figure 1.
Single-platelet biophysics highlight differences among common models of hemostasis and thrombosis. Although murine, canine, ovine, and human platelets adhere similar to fibrinogen (A) and collagen (B), porcine platelets exhibit the opposite pattern, in which adhesion to collagen is significantly higher than adhesion to fibrinogen. Bright-field images at original magnification of ×30 were obtained demonstrating stark differences in adhesion between human and porcine platelets. Bars represent 10 μm. Using the platelets from the adhesion assays, we measured their spreading area on fibrinogen (C) and collagen (D), normalizing the spreading area by dividing by the mean platelet volume (MPV). The accounting of the platelet volume showed that murine platelets spread to similar surface areas, as compared with human platelets on both fibrinogen and collagen. Compared with other species, ovine platelets exhibited increased spreading on those surfaces. Adhesion and spreading data are shown as median ± standard error of the mean (SEM; n = 4, 6, 6, 7, and 6 for humans, mice, dogs, pigs, and sheep, respectively). All species were compared with humans, and statistical significance was determined by 1-way ANOVA followed by Tukey’s multiple-comparisons test. *P ≤ .05, ***P ≤ .001, ****P ≤ .0001. (E) Platelets from dogs generated single-platelet forces that were 230% higher than that of human platelets, whereas ovine and murine platelets contracted the most similarly at 75% and 73% the force of human platelets, respectively. Representative single-platelet contraction confocal images are shown for each species, with a reference image. All species were compared with humans, and statistical significance was determined by mixed model, to account for within-subject variation. Bars represent 4 μm. Contraction force data are shown as median ± SEM (n = 8, 8, 7, 5, and 3 for humans, mice, dogs, pigs, and sheep, respectively). *P ≤ .05, ****P ≤ .0001. (F) Because our system allows for the generation of single-platelet forces at high throughput, force profiles generated for each species further highlight the stark differences between humans and dogs.

Single-platelet biophysics highlight differences among common models of hemostasis and thrombosis. Although murine, canine, ovine, and human platelets adhere similar to fibrinogen (A) and collagen (B), porcine platelets exhibit the opposite pattern, in which adhesion to collagen is significantly higher than adhesion to fibrinogen. Bright-field images at original magnification of ×30 were obtained demonstrating stark differences in adhesion between human and porcine platelets. Bars represent 10 μm. Using the platelets from the adhesion assays, we measured their spreading area on fibrinogen (C) and collagen (D), normalizing the spreading area by dividing by the mean platelet volume (MPV). The accounting of the platelet volume showed that murine platelets spread to similar surface areas, as compared with human platelets on both fibrinogen and collagen. Compared with other species, ovine platelets exhibited increased spreading on those surfaces. Adhesion and spreading data are shown as median ± standard error of the mean (SEM; n = 4, 6, 6, 7, and 6 for humans, mice, dogs, pigs, and sheep, respectively). All species were compared with humans, and statistical significance was determined by 1-way ANOVA followed by Tukey’s multiple-comparisons test. *P ≤ .05, ***P ≤ .001, ****P ≤ .0001. (E) Platelets from dogs generated single-platelet forces that were 230% higher than that of human platelets, whereas ovine and murine platelets contracted the most similarly at 75% and 73% the force of human platelets, respectively. Representative single-platelet contraction confocal images are shown for each species, with a reference image. All species were compared with humans, and statistical significance was determined by mixed model, to account for within-subject variation. Bars represent 4 μm. Contraction force data are shown as median ± SEM (n = 8, 8, 7, 5, and 3 for humans, mice, dogs, pigs, and sheep, respectively). *P ≤ .05, ****P ≤ .0001. (F) Because our system allows for the generation of single-platelet forces at high throughput, force profiles generated for each species further highlight the stark differences between humans and dogs.

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