Blood clots and thrombi consist primarily of a mesh of branched fibers made of the protein fibrin. We propose a molecular basis for the marked extensibility and negative compressibility of fibrin gels based on the structural and mechanical properties of clots at the network, fiber, and molecular levels. The force required to stretch a clot initially rises linearly and is accompanied by a dramatic decrease in clot volume and a peak in compressibility. These macroscopic transitions are accompanied by fiber alignment and bundling after forced protein unfolding. Constitutive models are developed to integrate observations at spatial scales that span six orders of magnitude and indicate that gel extensibility and expulsion of water are both manifestations of protein unfolding, which is not apparent in other matrix proteins such as collagen.Fibrin clots are proteinaceous gels that polymerize in the blood as a consequence of biochemical cascades at sites of vascular injury. Together with platelets, this meshwork stops bleeding and supports active contraction during wound healing (1,2). Fibrin also provides a scaffold for thrombi, clots that block blood vessels and cause tissue damage, leading to myocardial infarction, ischemic stroke, and other cardiovascular diseases (3). To maintain hemostasis while minimizing the impact of thrombosis, fibrin must have suitable stiffness and plasticity (4), but also sufficient permeability so that the network can be effectively decomposed (lysed) by proteolytic enzymes (5,6). It is challenging to meet all of these conditions because open scaffolds would be expected to break at low strains, as is true for collagen gels (7). To address how fibrin clots are both permeable and highly extensible, we studied fibrin structures across multiple spatial scales, from whole clots to single fibers and single molecules (Fig. 1).Fibrin clots were made from purified human fibrinogen under conditions (8) that resulted in the formation of long, straight fibers, similar to those found in physiological clots. To simplify the interpretation, the clots were covalently ligated with the use of a transglutaminase (blood clotting factor XIIIa), as naturally occurs in the blood, which prevents protofibrils from sliding past one another, thus eliminating persistent creep (9).Measurements of the extensibility of 2-mm-diameter fibrin clots ( Fig. 2A) demonstrated that the clots could be stretched to more than three times their relaxed length before breaking, with an average stretch of 2.7 ± 0.15-fold (n =6)(10). This is comparable to the single-fiber extensibility that is observed when a fibrin fiber is laterally stretched with an atomic force microscope (11). Qualitatively, the resulting force-strain curve for fibrin is similar to those observed for rubbers and other materials made from flexible chains (12). However, for fibrin clots, which are made of longer, straighter fibers than the thermally fluctuating polymer chains in rubber, models of rubber-like elasticity predict a branching density that is wro...

Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead‐based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.

The conjunction of insights from structural biology, solution biochemistry, genetics, and single-molecule biophysics has provided a renewed impetus for the construction of quantitative models of biological processes. One area that has been a beneficiary of these experimental techniques is the study of viruses. In this article we describe how the insights obtained from such experiments can be utilized to construct physical models of processes in the viral life cycle. We focus on dsDNA bacteriophages and show that the bending elasticity of DNA and its electrostatics in solution can be combined to determine the forces experienced during packaging and ejection of the viral genome. Furthermore, we quantitatively analyze the effect of fluid viscosity and capsid expansion on the forces experienced during packaging. Finally, we present a model for DNA ejection from bacteriophages based on the hypothesis that the energy stored in the tightly packed genome within the capsid leads to its forceful ejection. The predictions of our model can be tested through experiments in vitro where DNA ejection is inhibited by the application of external osmotic pressure.

A new generation of single-molecule experiments has opened up the possibility of reexamining many of the fundamental processes of biochemistry and molecular biology from a unique and quantitative perspective. One technique producing a host of intriguing results is the use of optical tweezers to measure the mechanical forces exerted by molecular motors during key processes such as the transcription of DNA or the packing of a viral genome into its capsid. The objective of the current article is to respond to such measurements on viruses and to use the theory of elasticity and a simple model of charge and hydration forces to derive the force required to pack DNA into a viral capsid as a function of the fraction of the viral genome that has been packed. The results are found to be in excellent accord with recent measurements and complement previous theoretical work. Because the packing of DNA in viral capsids occurs under circumstances of high internal pressure, we also compute how much pressure a capsid can sustain without rupture. In rapid succession over the last several years, a number of new experimental insights into the way DNA in viruses is packaged and ejected have been garnered. For example, the structure of both the portal motor (1) as well as an example of the membrane puncturing device that leads to the delivery of the viral genome have been determined (2). At lower resolution, results of cryoelectron microscopy experiments have revealed the structure of certain viruses at various stages during self-assembly (3) and the ordered arrangements of DNA in concentric circles within viral capsids (4-6). These insights have recently been complemented by single-molecule experiments in which the force exerted by the portal motor is measured during the process of viral packing itself (7).The problem of DNA packing is intriguing not only on the grounds of sheer geometric crowding, but also because of the recognition that the regions within which DNA is packaged (such as in a viral capsid) have linear dimensions that are comparable to the persistence length of the DNA, resulting in a steep elastic energy cost to be paid to effect such packing. The aim of this article is to take stock of the mechanical forces that come into play during viral packing and to reckon these forces explicitly in closed form in a simple model of DNA elasticity and interactions. These forces are then compared to those measured in fascinating recent single-molecule experiments on such packing (7). Because one of the conclusions to emerge from experiments, as well as models of the energetics of viral packing (8, 9), is that the viral capsid may be under pressures as high as 60 atmospheres, we also estimate the maximum pressure that such a capsid can sustain without rupturing.For the purposes of evaluating DNA packing forces, we take our cue from the structural insights into viral packing described above, cognizant, however, that the structural story is likely to be more complicated than the picture adopted here. In particular, we consider thre...