Shear-Mediated Platelet Activation is Accompanied by Unique Alterations in Platelet Release of Lipids.

INTRODUCTION: Platelet activation by mechanical means such as shear stress exposure, is a vital driver of thrombotic risk in implantable blood-contacting devices used in the treatment of heart failure. Lipids are essential in platelets activation and have been studied following biochemical activation. However, little is known regarding lipid alterations occurring with mechanical shear-mediated platelet activation. METHODS: Here, we determined if shear-activation of platelets induced lipidome changes that differ from those associated with biochemically-mediated platelet activation. We performed high-resolution lipidomic analysis on purified platelets from four healthy human donors. For each donor, we compared the lipidome of platelets that were non-activated or activated by shear, ADP, or thrombin treatment. RESULTS: We found that shear activation altered cell-associated lipids and led to the release of lipids into the extracellular environment. Shear-activated platelets released 21 phospholipids and sphingomyelins at levels statistically higher than platelets activated by biochemical stimulation. CONCLUSIONS: We conclude that shear-mediated activation of platelets alters the basal platelet lipidome. Further, these alterations differ and are unique in comparison to the lipidome of biochemically activated platelets. Many of the released phospholipids contained an arachidonic acid tail or were phosphatidylserine lipids, which have known procoagulant properties. Our findings suggest that lipids released by shear-activated platelets may contribute to altered thrombosis in patients with implanted cardiovascular therapeutic devices. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00692-x.

Shear-mediated platelet activation in the free flow II: Evolving mechanobiological mechanisms reveal an identifiable signature of activation and a bi-directional platelet dyscrasia with thrombotic and bleeding features.

Shear-mediated platelet activation (SMPA) in the "free flow" is the net result of a range of cell mechanobiological mechanisms. Previously, we outlined three main groups of mechanisms including: 1) mechano-destruction - i.e. additive platelet (membrane) damage; 2) mechano-activation - i.e. activation of shear-sensitive ion channels and pores; and 3) mechano-transduction - i.e. "outside-in" signaling via a range of transducers. Here, we report on recent advances since our original report which describes additional features of SMPA. A clear "signature" of SMPA has been defined, allowing differentiation from biochemically-mediated activation. Notably, SMPA is characterized by mitochondrial dysfunction, platelet membrane eversion, externalization of anionic phospholipids, and increased thrombin generation on the platelet surface. However, SMPA does not lead to integrin αIIbß3 activation or P-selectin exposure due to platelet degranulation, as is commonly observed in biochemical activation. Rather, downregulation of GPIb, αIIbß3, and P-selectin surface expression is evident. Furthermore, SMPA is accompanied by a decrease in overall platelet size coupled with a concomitant, progressive increase in microparticle generation. Shear-ejected microparticles are highly enriched in GPIb and αIIbß3. These observations indicate the enhanced diffusion, migration, or otherwise dispersion of platelet adhesion receptors to membrane zones, which are ultimately shed as receptor-rich PDMPs. The pathophysiological consequence of this progressive shear accumulation phenomenon is an associated dyscrasia of remaining platelets - being both reduced in size and less activatable via biochemical means - a tendency to favor bleeding, while concomitantly shed microparticles are highly prothrombotic and increase the tendency for thrombosis in both local and systemic milieu. These mechanisms and observations offer direct clinical utility in allowing measurement and guidance of the net balance of platelet driven events in patients with implanted cardiovascular therapeutic devices.

Human motion component and envelope characterization via wireless wearable sensors.

BACKGROUND: The characterization of limb biomechanics has broad implications for analyzing and managing motion in aging, sports, and disease. Motion capture videography and on-body wearable sensors are powerful tools for characterizing linear and angular motions of the body, though are often cumbersome, limited in detection, and largely non-portable. Here we examine the feasibility of utilizing an advanced wearable sensor, fabricated with stretchable electronics, to characterize linear and angular movements of the human arm for clinical feedback. A wearable skin-adhesive patch with embedded accelerometer and gyroscope (BioStampRC, MC10 Inc.) was applied to the volar surface of the forearm of healthy volunteers. Arms were extended/flexed for the range of motion of three different regimes: 1) horizontal adduction/abduction 2) flexion/extension 3) vertical abduction. Data were streamed and recorded revealing the signal "pattern" of movement in three separate axes. Additional signal processing and filtering afforded the ability to visualize these motions in each plane of the body; and the 3-dimensional motion envelope of the arm. RESULTS: Each of the three motion regimes studied had a distinct pattern - with identifiable qualitative and quantitative differences. Integration of all three movement regimes allowed construction of a "motion envelope," defining and quantifying motion (range and shape - including the outer perimeter of the extreme of motion - i.e. the envelope) of the upper extremity. The linear and rotational motion results from multiple arm motions match measurements taken with videography and benchtop goniometer. CONCLUSIONS: A conformal, stretchable electronic motion sensor effectively captures limb motion in multiple degrees of freedom, allowing generation of characteristic signatures which may be readily recorded, stored, and analyzed. Wearable conformal skin adherent sensor patchs allow on-body, mobile, personalized determination of motion and flexibility parameters. These sensors allow motion assessment while mobile, free of a fixed laboratory environment, with utility in the field, home, or hospital. These sensors and mode of analysis hold promise for providing digital "motion biomarkers" of health and disease.