Why Fibrin Biomechanical Properties Matter for Haemostasis and Thrombosis.

Polymeric fibrin displays unique structural and biomechanical properties that contribute to its essential role of generating blood clots that stem bleeds. The aim of this review is to discuss how the fibrin clot is formed, how protofibrils make up individual fibrin fibers, what the relationship is between the molecular structure and fibrin biomechanical properties, and how fibrin biomechanical properties relate to the risk of thromboembolic disease. Fibrin polymerization is driven by different types of bonds, including knob-hole interactions displaying catch-slip characteristics, and covalent crosslinking of fibrin polypeptides by activated factor XIII. Key biophysical properties of fibrin polymer are its visco-elasticity, extensibility and resistance to rupture. The internal packing of protofibrils within fibers changes fibrin biomechanical behavior. There are several methods to analyze fibrin biomechanical properties at different scales, including AFM force spectroscopy, magnetic or optical tweezers and rheometry, amongst others. Clinically, fibrin biomechanical characteristics are key for the prevention of thromboembolic disorders such as pulmonary embolism. Future studies are needed to address unanswered questions regarding internal molecular structure of the fibrin polymer, the structural and molecular basis of its remarkable mechanical properties and the relationship of fibrin biomechanical characteristics with thromboembolism in patients with deep vein thrombosis and ischemic stroke

Assembly of Miscible Supramolecular Network Blends Using DDA·AAD Hydrogen-Bonding Interactions of Pendant Side-Chains

The formation of polymer blends can result in materials with superior properties through combination of homo- or co-polymers with divergent functionalities. However, the contrasting physical properties of different polymers often result in phase separation. Herein we induce miscible blend formation of immiscible poly(methyl methacrylate) and polystyrene polymers through triple donor–donor–acceptor and acceptor–acceptor–donor (DDA·AAD) hydrogen bonding between complementary heterodimers on pendent side-chains. RAFT polymerization is used to synthesize a series of poly (methylmethacrylate) and polystyrene co-polymers bearing complementary side-chain hydrogen bonding motifs. Mixing of these polymers promoted miscible blend formation as demonstrated by atomic force microscopy and differential scanning calorimetry. The effectiveness of blend formation was shown to depend upon the extent of incorporation of hydrogen-bonding motif bearing co-monomer; lower degrees of incorporation lead to ineffective blending, whereas higher degree of incorporation, suppress phase separation and promote miscibility

Fibrinogen αC-subregions critically contribute blood clot fibre growth, mechanical stability, and resistance to fibrinolysis

Fibrinogen is essential for blood coagulation. The C-terminus of the fibrinogen α-chain (αC-region) is composed of an αC-domain and αC-connector. Two recombinant fibrinogen variants (α390 and α220) were produced to investigate the role of subregions in modulating clot stability and resistance to lysis. The α390 variant, truncated before the αC-domain, produced clots with a denser structure and thinner fibres. In contrast, the α220 variant, truncated at the start of the αC-connector, produced clots that were porous with short, stunted fibres and visible fibre ends. These clots were mechanically weak and susceptible to lysis. Our data demonstrate differential effects for the αC-subregions in fibrin polymerisation, clot mechanical strength, and fibrinolytic susceptibility. Furthermore, we demonstrate that the αC-subregions are key for promoting longitudinal fibre growth. Together, these findings highlight critical functions of the αC-subregions in relation to clot structure and stability, with future implications for development of novel therapeutics for thrombosis

Depth and medium-scale spatial processes influence fish assemblage structure of unconsolidated habitats in a subtropical marine park

Where biological datasets are spatially limited, abiotic surrogates have been advocated to inform objective planning for Marine Protected Areas. However, this approach assumes close correlation between abiotic and biotic patterns. The Solitary Islands Marine Park, northern NSW, Australia, currently uses a habitat classification system (HCS) to assist with planning, but this is based only on data for reefs. We used Baited Remote Underwater Videos (BRUVs) to survey fish assemblages of unconsolidated substrata at different depths, distances from shore, and across an along-shore spatial scale of 10 s of km (2 transects) to examine how well the HCS works for this dominant habitat. We used multivariate regression modelling to examine the importance of these, and other environmental factors (backscatter intensity, fine-scale bathymetric variation and rugosity), in structuring fish assemblages. There were significant differences in fish assemblages across depths, distance from shore, and over the medium spatial scale of the study: together, these factors generated the optimum model in multivariate regression. However, marginal tests suggested that backscatter intensity, which itself is a surrogate for sediment type and hardness, might also influence fish assemblages and needs further investigation. Species richness was significantly different across all factors: however, total MaxN only differed significantly between locations. This study demonstrates that the pre-existing abiotic HCS only partially represents the range of fish assemblages of unconsolidated habitats in the region

Biogeographical and cross-shelf patterns of reef fish assemblages in a transition zone

Transition zones have complex patterns of biogeography and biodiversity which require consideration in conservation planning. Cross-shelf patterns of reef fish assemblage structure and biogeographic representation were determined for the Solitary Islands Marine Park (SIMP), positioned in a tropical-temperate overlap on the east coast of Australia. Sixty-eight sites were surveyed on shallow (\u3c25 m) reefs across an inshore–offshore gradient, using timed counts. Tropical taxa were most prevalent, comprising 50% of the 254 species recorded. Australian endemics accounted for 23% of species, with east coast endemics (14%) predominating. There was a strong cross-shelf gradient, with species richness increasing offshore. There was also a distinct biogeographical gradient with the proportion of temperate species decreasing and tropical species increasing with increasing distance from shore. This gradient was similar for endemic and cosmopolitan species as many of the endemics were temperate or subtropical, and many of the tropical species were widespread Indo-Pacific taxa. These patterns are consistent with sites further offshore being more frequently exposed to the tropical East Australian Current (EAC). Patterns on reefs further inshore are consistent with the high levels of endemism previously reported for temperate and subtropical Australian waters. The complex cross-shelf arrangement of tropical, subtropical and temperate species results in high regional biodiversity and needs to be recognised in marine-park planning