Blood Plasma Proteins Research Articles

Фракційний склад білків крові коропа за дії хлортетрацикліну, нандролону та альбендазолу

<p>The influence of xenobiotics, in particular, the antibiotic chlortetracycline, anabolic steroid nandrolone and anthelmintic albendazole, on carp fish depends on their concentration in water and is associated with a change in a number of morphological indices and physiological and biochemical mechanisms in the process of their adaptation to the action of xenobiotics of water, and as shown by the study - total content and fractional composition of blood plasma proteins. In model experiments carried out on the bogs of carp, the main objective of which was to investigate the influence of xenobiotics of anthropogenic origin on the fractional composition of plasma proteins, it was established that for a short exposure (72 hours) and low concentrations of nandrolone 0.1 mg / dm3 (the first experimental group) and (0.5 mg / dm3 second experimental group), only slight changes in the protein content with a molecular weight of 25, 35-50 and 100-140 kDa in the water of the aquariums are observed at constant values of the parameters of other fractions. With an increase in the concentration of nandrolone in aquarium water up to 1.0 mg / dm3, the protein content with a molecular weight of 450 kDa and above increased by 91%, 340 kDa by 78%, 260 kDa by 101%, 70 kDa by 149%, 50 kDa - 111%, 25-50 kDa - 35-62% compared to control. Consequently, anabolic steroids, getting into the water at low concentrations do not affect, and in high stimulate biosynthesis processes of proteins in tissues, two decades of carp.</p><p>The intolerance (12 hours) of carps in an aquarium with an anthelmintic concentration of albendazole in water of 0.2 mg / L varied only with individual fractions of blood plasma proteins of fish. The increase in the concentration of albendazole in water to 0.5 mg / L and especially to 1.0 mg / L affects the protein spectrum of blood plasma fish to a large extent, reducing the content of most proteins of low and high molecular weight fractions. It was found that chlortetracycline in the concentration of 1.10 mg / dm3 did not affect, and when it increased in water to 3.15 and 6.30 mg / dm3, it reduced the level of proteins in the blood plasma of the carp in 3 days, with a molecular weight of 340-450 kDa, and higher and contributed to the appearance of protein fractions with a molecular weight of 140 - 200 and 70 - 90 kDa. Investigated xenobiotics chlortetracycline, nandrolone and albendazole, in the above-mentioned concentrations in water and short-term exposure of fish, did not affect their behavior, the number of respiratory movements and the tomographic indices of the internal organs. The state of the external body covers, as well as the organoleptic indices of the internal organs of fish of experimental groups for the effects of various concentrations of the studied xenobiotics, did not differ from the similar characteristics of the control group carps. The obtained results testify to the important role of blood plasma proteins in the mechanisms of their adaptation to the action of xenobiotics of water, in particular anabolic steroid nandrolone, antibiotic chlortetracycline and anthelmintic albendazole. </p>

Neurofilament light protein in blood predicts regional atrophy in Huntington disease.

ObjectiveNeurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.MethodsWe examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers.ResultsAfter controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression.ConclusionsThese findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.

OXIDATIVE STRESS AND EARLY POST-OPERATIVE COMPLICATIONS IN CARDIAC SURGERY

Cardiac surgery is often complicated by oxidative stress (the evidence of this is the increase of carbonyl proteins in blood plasma), however the relation between these changes and post-operative complications and unfavorable outcomes stills remains uninvestigated and lacks the relevant proof. The above facts served as basis for this research. Goal of the article: to investigate the impact of oxidative stress assessed as per the level of carbonyl proteins in blood plasma on systemic inflammation response syndrome (SIRS), acute heart (AHF) and renal failure (ARF) in cardiac surgery. Methods. Prospective observational cohort study was conducted in order to investigate the relation of oxidative stress intensity, assessed as per the level of carbonyl peptides in blood plasma, and development of SIRS, AHF, ARF in the patients undergoing cardiac surgery. 67 adults patients admitted to Cardiac Intensive Care Department of M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, were examined. Results. The significant positive correlation has been found between intensity of oxidative stress assessed as per the level of carbonyl peptides in blood plasma, and composite frequency of post-operative complications (SIRS, AHF and ARF) in cardiac surgery (Spearman rank correlation (r) = 0.6; p < 0.0001). It was found out that the area under ROC-curve made 0.81 and 0.83 for the risk of developing acute renal lesions and heart failure respectively (p < 0.01 in both cases) thus the investigated model can be evaluated as a model of very good quality. Conclusion. The important role pf oxidative stress in the development of SIRS, AHF and ARF has been confirmed. No advantages of off pump technique when performing coronary artery bypass grafting have been detected. Testing carbonyl peptides in blood plasma during first hours after surgery can be recommended in order to predict the risk of developing SIRS, AHF and ARF.

Adsorption of Bovine Serum Albumin on Carbon-Based Materials

The protein adsorption plays a very important role in biotechnology, biomolecular engineering and it is one of the main factors determining bio- and hemocompatibility of biomedical materials in medical applications, such as blood purification and wound healing. Here we report adsorption properties of two carbon-based materials, thermally expanded graphite (EGr) and graphene nanoplatelets (GnP), for bovine serum albumin (BSA), the most abundant blood plasma protein. The influence of the surface chemistry of expanded graphite on the mechanism of BSA adsorption was studied by using EGr modified with oxygen or nitrogen functionalities. Having low microporosity and the specific surface area in the range of 5 to 50 m2/g, the expanded graphite exhibits high protein adsorption capacity at high equilibrium concentrations, which makes this material a potential candidate for biomedical applications as a carrier for high molecular weight (HMW) drug delivery or adsorption of HMW metabolites. At low equilibrium concentrations, the effect of specific protein-surface functional groups interaction reveals the differences between the adsorption affinity of different surface modified EGr materials to BSA. The adsorption of BSA on GnP with a specific surface area of 286 m2/g and a developed micro-/mesoporous structure did not follow the same mechanism as seen with EGr materials. At low equilibrium concentration of BSA, GnP exhibits high adsorption efficiency. An important finding is that no release of nanoparticles from expanded graphite adsorbents was observed, which makes them potentially suitable for direct contact with blood and other tissues while very small nanoparticles were noticed in the case of graphene nanoplatelets.

Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins - the introduction of protein-corona-free polymer nanomedicine.

In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA): a block copolymer, poly(ε-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry, dynamic light scattering, and cryo-transmission electron microscopy. The copolymers were labeled with TEMPO radicals at the end of hydrophobic PCL or along the hydrophilic HPMA chains to monitor changes in polymer chain dynamics caused by protein adsorption. By EPR and other methods, we were able to probe specific interactions between nanoparticles and blood proteins, specifically low- and high-density lipoproteins, immunoglobulin G, human serum albumin (HSA), and human plasma. It was found that individual proteins and plasma have very low binding affinity to nanoparticles. We observed no hard corona around HPMA-based nanoparticles; with the exception of HSA the proteins showed no detectable binding to the nanoparticles. Our study confirms that a classical "hard corona-soft corona" paradigm is not valid for all types of nanoparticles and each system has a unique protein corona that is determined by the nature of the NP material.

Interactions Between Plant Viral Nanoparticles (VNPs) and Blood Plasma Proteins, and Their Impact on theVNP In Vivo Fates.

Plant viral nanoparticles (VNPs) are currently being developed as novel vessels for delivery of diagnostic and therapeutic cargos to sites of disease. With a rapid increase in the number of VNP variants and their potential applications in nanomedicine, the properties they acquire in the bloodstream need to be investigated. Biomolecules present in plasma are known to adsorb onto the surface of nanomaterials (including VNPs), forming a biointerface called the protein corona, which is capable of reprogramming the properties of VNPs. Here we describe a few general methods to isolate and study the VNP-protein corona complexes, in order to evaluate the impact of protein corona on molecular recognition of VNPs by target cells, and clearance by phagocytes. We outline procedures for in vivo screening of VNP fates in a mouse model, which may be useful for evaluation of efficacy and biocompatibility of different VNP based formulations.

Characterization of mercury-binding proteins in rat blood plasma.

Mercury-binding protein profiles in rat plasma at different levels of mercury exposure in vitro and in vivo were systematically investigated using column gel electrophoresis coupled with inductively coupled plasma-mass spectrometry. The current finding provided various protein candidates that may play critical roles in mercury binding and transporting in plasma.

Tannic acid-loaded mesoporous silica for rapid hemostasis and antibacterial activity

Massive blood loss and bacterial infection are major challenges for global public health. In this study, we developed tannic acid (TA)-loaded mesoporous silica (MS) nanoparticles for both hemorrhage control and effective antibacterium via covalent conjugation and electrostatic adsorption. The TA-absorbed MS could significantly relieve hemolysis and facilitate blood contact, therefore efficiently promoting protein adhesion and the contact activation pathway of the coagulation cascade with desirable hemostasis. Comparably, with increasing TAs absorption, the bleeding control and antibacterial performance were improved simultaneously, especially for 15TMS. Hemostasis tests demonstrated that the 15TMS could reduce the hemostatic time by 65% both in vitro and in vivo, with lower blood loss and could exhibit better antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis as well as promote wound healing. However, the TAs-loaded MS via chemical grafting (15T-g-MS) significantly reduced the surface area of MS, by replacing the Si-OH on the MS, and thus it exhibited worse bleeding control and antibacterial efficacy than 15TMS. Furthermore, all the samples exhibited excellent cell viability. Based on these results, it can be concluded that the 15TMS would be a promising material platform for designing hemostats in more extensive clinical application.

ANTIPHOSPHOLIPID SYNDROME

Antiphospholipid syndrome is autoimmune acquired thrombophilia associated with the formation of antibodies to phospholipids, which is manifested by recurrent venous or arterial thrombosis and/or pathology of pregnancy. Antiphospholipid antibodies are a heterogeneous group of autoantibodies interacting with phospholipids, which are components of cell membranes and phospholipid-binding proteins of blood plasma. Antiphospholipid syndrome can affect vessels of any caliber and localization, with thrombosis accompanied by no morphological signs of inflammation in the wall of the vessel. Obstetrical pathology is manifested by loss of the fetus, which can occur at any time of pregnancy, as well as other complications of pregnancy, such as preeclampsia and placental insufficiency. Based on the classification criteria, antiphospholipid syndrome is diagnosed if one of the clinical criteria (thrombosis or pregnancy complication) and one of the laboratory criteria including the lupus anticoagulant, antibodies to cardiolipin or β2-glycoprotein I, are revealed. The main tactic of the treatment of patients with antiphospholipid syndrome is to prevent thrombosis. For this purpose, the traditional therapy with anticoagulants and antiaggregants is applied. In addition, new medicines are being developed and evaluated

Nitric oxide releasing vascular catheters for eradicating bacterial infection.

The interaction of blood proteins with an implant surface is not only a fundamental phenomenon but is also key to several important medical complications. Plasma proteins binding on the surface of intravascular catheters can promote bacterial adhesion leading to the risk of local and systemic complications such as catheter-related blood infections (CRBIs). The incidences of CRBIs in the United States amount to more than 250,000 cases/year with an attributable mortality of up to 35% and an annual healthcare expenditure of $2.3 billion approximately. This demands the development of truly nonthrombogenic and antimicrobial catheters. In the present study, catheters were fabricated by incorporating a nitric oxide (NO) donor molecule, S-nitroso-N-acetyl-penicillamine (SNAP) in a hydrophobic medical grade polymer, Elasteon-E2As. NO offers antithrombotic and antibacterial attributes without promoting drug resistance and cytotoxicity. E2As-SNAP catheters were first coated with fibrinogen, a blood plasma protein plays a key role in clot formation and eventual bacterial adhesion to the implant surface. The suitability of the catheters for biomedical applications was tested in vitro for contact angle, NO release kinetics, inhibition of bacteria, and absence of cytotoxicity toward mammalian cells. The highly hydrophobic catheters released NO in the physiological range that inhibited >99% bacterial viability on fibrinogen-coated catheters in a 24 h study. No toxic response of E2As-SNAP catheters leachate was observed using a standard cytotoxicity assay with mouse fibroblast cells. Overall, the results showed that the E2As-SNAP catheters can inhibit viable bacteria even in the presence of blood proteins without causing a cytotoxic response. The fundamentals of this study are applicable to other blood-contacting medical devices as well. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2849-2857, 2018.

Phenelzine reduces the oxidative damage induced by peroxynitrite in plasma lipids and proteins

Peroxynitrite is a reactive nitrogen species produced in the intravascular compartment from superoxide anion and nitric oxide. Peroxynitrite destroys blood plasma proteins and membranes of red blood cells and of platelets. This explains why excessive production of peroxynitrite contributes to diseases and to ageing. Therapeutics that antagonize peroxynitrite may delay ageing and the progression of disease. We developed an in vitro assay that allows the investigation of the oxidative damage caused by peroxynitrite in the intravascular compartment. This assay correlates the damage with the rate of formation of protein carbonyl groups, 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances. Using this assay, we evaluated the ability of phenelzine, a scavenger of reactive aldehydes, to antagonize the effects of peroxynitrite. Herein, we showed that phenelzine significantly decreased the lipid peroxidative damage caused by peroxynitirite in blood plasma and platelets. Moreover, it inhibited carbonyl group and 3-NT formation in blood plasma and platelet proteins.

Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice.

Aging progression is a process that an individual encounters as they become older, and usually results from a series of normal physiological changes over time. The hippocampus, which contributes to the loss of spatial and episodic memory and learning in older people, is closely related to the detrimental effects of aging at the morphological and molecular levels. However, age-related genetic changes in hippocampal molecular mechanisms are not yet well-established. To provide additional insight into the aging process, differentially-expressed genes of 3- versus 24- and 29-month old mice were re-analyzed. The results revealed that a large number of immune and inflammatory response-related genes were up-regulated in the aged hippocampus, and membrane receptor-associated genes were down-regulated. The down-regulation of transmembrane receptors may indicate the weaker perception of environmental exposure in older people, since many transmembrane proteins participate in signal transduction. In addition, molecular interaction analysis of the up-regulated immune genes indicated that the hub gene, Ywhae, may play essential roles in immune and inflammatory responses during aging progression, as well as during hippocampal development. Our biological experiments confirmed the conserved roles of Ywhae and its partners between human and mouse. Furthermore, comparison of microarray data between advanced-age mice treated with human umbilical cord blood plasma protein and the phosphate-buffered saline control showed that the genes that contribute to the revitalization of advanced-age mice are different from the genes induced by aging. These results implied that the revitalization of advanced-age mice is not a simple reverse process of normal aging progression. Our data assigned novel roles of genes during aging progression and provided further theoretic evidence for future studies exploring the underlying mechanisms of aging and anti-aging-related disease therapy.

Interactions of liposomes carrying lipophilic prodrugs in the bilayer with blood plasma proteins

Interactions of 100-nm liposomes prepared from egg yolk phosphatidylcholine and baker’s yeast phosphatidylinositol carrying diglyceride ester conjugates of melphalan (Mlph-liposomes) and methotrexate (MTX-liposomes) in the bilayer with blood plasma proteins were studied with Western blotting. Earlier hemocompatibility tests have demonstrated that the liposomes did not affect main blood cells, but MTX-liposomes, and not Mlph-liposomes, induced complement (C) activation in vitro. Here, we show that introduction of polyethylene glycol conjugate (instead of phosphatidylinositol as a stabilizing lipid) or a targeting carbohydrate conjugate has little effect on interaction of Mlph-liposomes with major C components and apolipoproteins, as well as the total protein binding ability of the liposomes. Liposomes loaded with Mlph prodrug did not trigger fragmentation of C3 protein, the central component of the complement, while MTX-liposomes did so, which agrees with our previous findings. Analysis of MTX-liposome binding with C3 protein and its fragments, regulatory C proteins, and immunoglobulins allowed for the conclusion that MTX-liposomes activate complement via the alternative activation pathway. As shown earlier, the decrease in the prodrug concentration in the bilayer to the level corresponding to MTX low-dose treatment regimen allows avoiding C activation.

Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging.

Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals. Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals. Both tracers did not bind to blood cells. [68Ga]DPTA but not [68Ga]EDTA showed strong binding to plasma proteins. For this reason, [68Ga]DPTA stayed much longer in the blood and only 30% of the injected dose was eliminated by the kidney within 60min whereas the excretion of [68Ga]EDTA was 89±1%. The calculated GFR using [68Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [68Ga]-DPTA, the measurements led to values which were 80% below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR. [68Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [68Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.

Platelet Adhesion and Activation on Chiral Surfaces: The Influence of Protein Adsorption.

Adsorbed proteins and their conformational change on blood-contacting biomaterials will determine their final hemocompatibility. It has frequently been reported that surface chirality of biomaterials may highly influence their protein adsorption behavior. Here, lysine and tartaric acid with different chirality were immobilized onto TiO2 films respectively, and the influence of surface chirality on protein adsorption, platelet adhesion, and activation was also investigated. It showed that the l- and d-molecule grafted samples had almost the same grafting density, surface topography, chemical components, and hydrophilicity in this study. However, biological behaviors such as protein adsorption, platelet adhesion, and activation were quite different. The d-lysine grafted surface had a greater ability to inhibit both bovine serum albumin and fibrinogen adsorption, along with less degeneration of fibrinogen compared to the l-lysine anchored surface. However, the d-tartaric acid grafted surface adsorbed more protein but with less denatured fibrinogen compared to the l-tartaric acid grafted one. Further studies showed that the secondary structural change of the adsorbed albumin and fibrinogen on all surfaces with deduction of the α-helix content and increase of disordered structure, while the changing degree was apparently varied. As a result, the d-lysine immobilized surface absorbed less platelets and red blood cells and achieved slightly increased platelet activation. For tartaric acid anchored surfaces, a larger number of platelets adhered to the D-surface but were less activated compared to the L-surface. In conclusion, the surface chirality significantly influenced the adsorption and conformational change of blood plasma protein, which in turn influenced both platelet adhesion and activation.

Detonation nanodiamonds as antioxidants in various test systems

Detonation nanodiamonds (DND) are shown to exhibit antioxidant activity both in vitro and in vivo. DNDs, when introduced into laboratory animals by oral delivery, decrease protein peroxidation in erythrocytes, inhibit peroxidation of lipids and proteins in blood plasma. In case a pro-oxidant, NaNO2, is administered to animals, DND also protects them against the chemically induced oxidative stress. The results of the testing provide the experimental basis for recommending DND as a potential antioxidant for correcting oxidative damage of different origin.

Comparatyive determination of proteins, nitrogen-containing compounds and lipids content in blood plasma and ascitic fluid in patients with liver cirrhosis

The aim of the work is the determination of proteins concentration in blood plasma and ascetic fluid and also toxic and atherogenic properties of ascitic fluid in patients with different stages of liver cirrhosis for the further choice of the individual treating tactics.Research methods: 262 patients with liver cirrhosis, according to the diagnostic examination, who demonstrated the different severity of the pathological process in the liver parenchyma, were divided in 4 groups. In blood plasma and ascitic fluid of patients with liver cirrhosis were determined the concentration of protein, general content of bilirubin, concentration of final nitrogen, creatinine, urea, cholesterol and lecithin. Results: the obtained results demonstrate the disorder of the protein homeostasis and increase of the content of atherogenic lipoproteins, as a result of which hepatocyte membrane structures in patients with liver cirrhosis are destructed. The content of studied components in ascitic fluid was identical (and sometimes even more) to the one in blood plasma – it allows to consider ascitic fluid as a plasma-replacing component in patients with liver cirrhosis, especially at the hepatic failure progression.The degree of the disorder of the functional activity of the liver parenchyma was studied. The author of the article concludes that at choosing the surgical tactics in patients with liver cirrhosis, complicated with acsites, the degree of homeostasis disorders expressiveness must be taken into account

Оценка взаимодействия окисленного графена с мембранами эритроцитов и белками плазмы крови крыс методом спиновых зондов

Оценка взаимодействия окисленного графена с мембранами эритроцитов и белками плазмы крови крыс методом спиновых зондов

One‐Step Noncovalent Surface Functionalization of PDMS with Chitosan‐Based Bioparticles and Their Protein‐Repellent Properties

AbstractStable hydrophilic and protein‐repellent surfaces from nontoxic polysaccharides are highly desirable in several biomedical applications such as implants and prosthetics. Herein, a water‐based one‐step strategy to functionalize polydimethylsiloxane (PDMS) surfaces with chitosan‐based bioparticles is described to suppress the adsorption of blood plasma proteins, which causes biofilm formation and implant‐associated infection. Micro‐ and nanosized chitosan (Chi) and carboxymethyl chitosan (CMChi) particles, featuring high stability, hydrophilicity, and zwitterionic feature, are synthesized in an ecofriendly solvent water and their interaction with PDMS surfaces is investigated in‐real time over a wide range of pH (3–10) using a quartz crystal microbalance with dissipation (QCM‐D). The results show that both Chi and CMChi form stable colloidal particles at pH close to their zero‐point charge, and thus exhibit maximum adsorption and irreversibly bound layers on PDMS surfaces. Coating from CMChi shows high stability, improved hydrophilicity, and subsequently no adsorption of bovine serum albumin and enhanced resistance to fibrinogen, compared to Chi and native PDMS, as revealed by water contact angle and QCM‐D measurements. The results demonstrate the possibility to develop novel and biobased coating materials to address unspecific protein adsorption not only on silicone‐based implants but also on other biomaterials in general.

Conformational Flexibility and Self-Association of Fibrinogen in Concentrated Solutions.

We studied the hydrodynamic behavior of fibrinogen, a blood plasma protein involved in blood clotting, in a broad 0.3-60 mg/mL range of concentration and 5-42 °C temperature using pulsed-field gradient 1H NMR-diffusometry. Arrhenius plots revealed the activation energy for fibrinogen diffusion Ed = 21.3 kJ/mol at 1.4 mg/mL and 28.4 kJ/mol at 38 mg/mL. We found a dramatic slowdown in fibrinogen self-diffusion with concentration beginning at 1.7-3.4 mg/mL, which deviated from the standard hard-particle behavior, suggesting a remarkable intermolecular entanglement. This concentration dependence was observed regardless of the absence or presence of the GPRP peptide (inhibitor of fibrin polymerization), and also in samples free of fibrin oligomers. By contrast, diffusivity of fibrinogen variant I-9 with truncated C-terminal portions of the Aα chains was much less concentration-dependent, indicating the importance of intermolecular linkages formed by the αC regions. Theoretical models combined with all-atom molecular dynamics simulations revealed partially bent fibrinogen solution conformations that interpolate between a flexible chain and a rigid rod observed in the crystal. The results obtained illuminate the important role of the αC regions in modulating the fibrinogen molecular shape through formation of weak intermolecular linkages that control the bulk properties of fibrinogen solutions.