RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means.

Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5'-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions.

Clots reveal anomalous elastic behavior of fiber networks.

The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers.

Prospection of Peptide Inhibitors of Thrombin from Diverse Origins Using a Machine Learning Pipeline.

Thrombin is a key enzyme involved in the development and progression of many cardiovascular diseases. Direct thrombin inhibitors (DTIs), with their minimum off-target effects and immediacy of action, have greatly improved the treatment of these diseases. However, the risk of bleeding, pharmacokinetic issues, and thrombotic complications remain major concerns.

Hyperbaric treatment of platelets is comparable to cold storage alone over 14 days.

Background: Platelets stored at room temperature (22-24°C) for transfusion purposes have a shelf life of 5-7 days, or 72 h when stored refrigerated (1-6°C). The limited shelf life of platelet products severely compromises platelet inventory. We hypothesized that cold storage of platelets in 100% plasma using xenon gas under high pressure would extend shelf life to 14 days.

A low-cost, high-throughput microfluidic nano-culture platform for functional metagenomics.

Functional metagenomics is an attractive culture-independent approach for functional screening of diverse microbiomes to identify known and novel genes. Since functional screening can involve sifting through tens of thousands of metagenomic library clones, an easy high-throughput screening approach is desirable. Here, we demonstrate a proof-of-concept application of a low-cost, high-throughput droplet based microfluidic assay to the selection of antibiotic resistance genes from a soil metagenomic library.

The interaction of vortical flows with red cells in venous valve mimics.

The motion of cells orthogonal to the direction of main flow is of importance in natural and engineered systems. The lateral movement of red blood cells (RBCs) distal to sudden expansion is considered to influence the formation and progression of thrombosis in venous valves, aortic aneurysms, and blood-circulating devices and is also a determining parameter for cell separation applications in flow-focusing microfluidic devices. Although it is known that the unique geometry of venous valves alters the blood flow patterns and cell distribution in venous valve sinuses, the interactions between fluid flow and RBCs have not been elucidated.

Identification of Distinct Characteristics of Antibiofilm Peptides and Prospection of Diverse Sources for Efficacious Sequences.

A majority of microbial infections are associated with biofilms. Targeting biofilms is considered an effective strategy to limit microbial virulence while minimizing the development of antibiotic resistance. Toward this need, antibiofilm peptides are an attractive arsenal since they are bestowed with properties orthogonal to small molecule drugs.

-Adventitial delivery of smooth muscle cells in porous collagen scaffolds for treatment of experimental abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is associated with the loss of vascular smooth muscle cells (SMCs) within the vessel wall. Direct delivery of therapeutic cells is challenging due to impaired mechanical integrity of the vessel wall. We hypothesized that porous collagen scaffolds can be an effective vehicle for the delivery of human-derived SMCs to the site of AAA.

Fibrin prestress due to platelet aggregation and contraction increases clot stiffness.

Efficient hemorrhagic control is attained through the formation of strong and stable blood clots at the site of injury. Although it is known that platelet-driven contraction can dramatically influence clot stiffness, the underlying mechanisms by which platelets assist fibrin in resisting external loads are not understood. In this study, we delineate the contribution of platelet-fibrin interactions to clot tensile mechanics using a combination of new mechanical measurements, image analysis, and structural mechanics simulation.

Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days.

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days.

Nicotine Affects Murine Aortic Stiffness and Fatigue Response During Supraphysiological Cycling.

Nicotine exposure is a major risk factor for several cardiovascular diseases. Although the deleterious effects of nicotine on aortic remodeling processes have been studied to some extent, the biophysical consequences are not fully elucidated. In this investigation, we applied quasi-static and dynamic loading to quantify ways in which exposure to nicotine affects the mechanical behavior of murine arterial tissue.

A Facile High-Throughput Model of Surface-Independent Staphylococcus aureus Biofilms by Spontaneous Aggregation.

Many microbes in their natural habitats are found in biofilm ecosystems attached to surfaces and not as free-floating (planktonic) organisms. Furthermore, it is estimated that nearly 80% of human infections are associated with biofilms. Biofilms are traditionally defined as three-dimensional, structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material.

Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways.

Background: Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days.

Study Design And Methods: This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis.

Automated Motion Tracking and Data Extraction for Red Blood Cell Biomechanics.

Red blood cell biomechanics can provide us with a deeper understanding of macroscopic physiology and have the potential of being used for diagnostic purposes. In diseases like sickle cell anemia and malaria, reduced red blood cell deformability can be used as a biomarker, leading to further assays and diagnoses. A microfluidic system is useful for studying these biomechanical properties.

CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata.

Candida glabrata is a human commensal and an opportunistic human fungal pathogen. It is more closely related to the model yeast Saccharomyces cerevisiae than other Candida spp. Compared with S.

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles.

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration.

Image-based analysis and simulation of the effect of platelet storage temperature on clot mechanics under uniaxial strain.

Optimal strength and stability of blood clots are keys to hemostasis and in prevention of hemorrhagic or thrombotic complications. Clots are biocomposite materials composed of fibrin network enmeshing platelets and other blood cells. We have previously shown that the storage temperature of platelets significantly impacts clot structure and stiffness.

Nano-biofilm Arrays as a Novel Universal Platform for Microscale Microbial Culture and High-Throughput Downstream Applications.

Biofilms are the predominant mode of microbial growth and it is now fully accepted that a majority of infections in humans are associated with a biofilm etiology. Biofilms are defined as attached and structured microbial communities surrounded by a protective exopolymeric matrix. Importantly, sessile microorganisms growing within a biofilm are highly resistant to antimicrobial agents.

Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome.

Background: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease.

An Automated Algorithm to Quantify Collagen Distribution in Aortic Wall.

Arterial diseases including abdominal aortic aneurysm and atherosclerosis are biomechanical diseases characterized by significant changes in the structure and strength of the vessel wall. It is now established that local variations in fibrillar collagen and elastin matrix turnover is critical to arterial stiffening and progression of the disease. The collagen content in the aortic wall has nominally been quantified by biochemical assays and immunohistochemical analysis as the total amount because of the difficulty in separating the media and adventitia.

Antimicrobial and Antibiofilm Activity of Synergistic Combinations of a Commercially Available Small Compound Library With Colistin Against .

Biofilm-associated infections remain a significant clinical challenge since the conventional antibiotic treatment or combination therapies are largely ineffective; and new approaches are needed. To circumvent the major challenges associated with discovery of new antimicrobials, we have screened a library of compounds that are commercially available and approved by the FDA (Prestwick Chemical Library) against for effective antimicrobial and anti-biofilm activity. A preliminary screen of the Prestwick Chemical Library alone did not yield any repositionable candidates, but in a screen of combinations with a fixed sub-inhibitory concentration of the antibiotic colistin we observed 10 drugs whose bacterial inhibiting activity was reproducibly enhanced, seven of which were enhanced by more than 50%.

An In Vitro Model for Biofilms on Titanium Surfaces.

The oral cavity serves as a nutrient-rich haven for over 600 species of microorganisms. Although many are essential to maintaining the oral microbiota, some can cause oral infections such as caries, periodontitis, mucositis, and endodontic infections, and this is further exacerbated with dental implants. Most of these infections are mixed species in nature and associated with a biofilm mode of growth.

Core-shell magnetoelectric nanorobot - A remotely controlled probe for targeted cell manipulation.

We have developed a remotely controlled dynamic process of manipulating targeted biological live cells using fabricated core-shell nanocomposites, which comprises of single crystalline ferromagnetic cores (CoFeO) coated with crystalline ferroelectric thin film shells (BaTiO). We demonstrate them as a unique family of inorganic magnetoelectric nanorobots (MENRs), controlled remotely by applied a.c.

Influence of membrane cholesterol on monocyte chemotaxis.

Cholesterol content influences several important physiological functions due to its effect on membrane receptors. In this work, we tested the hypothesis that cellular cholesterol alters chemotactic response of monocytes to Monocyte Chemoattractant Protein-1 (MCP-1) due to their effect on the receptor, CCR2. We used Methyl-β-cyclodextrin (MβCD) to alter the baseline cholesterol in human monocytic cell line THP-1, and evaluated their chemotactic response to MCP-1.