Tatiana Mencarini, Yana Roka-Moiia, Eleonora Puce, Anna Zucchi, Silvia Bozzi, Alberto Redaelli, Marvin J Slepian
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引用次数: 0
Abstract
Introduction: Platelet adhesion and aggregation on exposed vascular extracellular matrix (ECM) is critical for haemostasis, with dysregulation and inappropriate thrombus formation associated with cardiovascular disease. While collagen is recognised as vital in these processes, the role of other ECM proteins is less understood. Platelet-derived microparticles (PDMPs), small vesicles released by activated platelets, similarly influence haemostasis, though their modulatory effect on ECM substrates is also unclear. We investigated platelet adhesion and aggregation on various ECM proteins-collagen, fibrinogen, fibronectin, and laminin-and examined the modulatory role of PDMPs under physiologic and pathologic flow conditions.
Methods: Whole blood, alone or enriched with PDMPs, was perfused through microfluidic channels coated with ECM substrates at varying shear rates. Fluorescence imaging assessed platelet behaviour measuring surface coverage, number of thrombi, mean thrombus area and thrombus height.
Results: Collagen exhibited greatest overall thrombus formation, versus the other ECM substrates, with platelet adhesion and aggregation increasing at higher shear rates. Addition of PDMPs significantly reduced thrombus area (p < 0.01) and height (p < 0.05-0.01) at all shear rates. Fibrinogen supported stable but smaller thrombi, with PDMP addition resulting in increased platelet adhesion (23% increase) at low shear. Both fibronectin and laminin demonstrated weak platelet adhesion, with thrombus formation decreasing as shear rate increased, and PDMP addition slightly increasing platelet adhesion, though without influence on thrombus dimensions.
Conclusion: Collagen exerts a dominant effect in platelet adhesion and aggregation across a wide range of shear, compared to fibrinogen, fibronectin and laminin. PDMPs alter platelet adhesion and resultant thrombus formation across all ECM proteins tested, likely through competitive occupation of platelet binding sites. Our findings underscore the complex interactions between ECM proteins, PDMPs, and shear forces under flow conditions.
Supplementary information: The online version contains supplementary material available at 10.1007/s12195-026-00920-2.
期刊介绍：
The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas:
Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example.
Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions.
Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress.
Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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