Nonlinear elasticity of stiff biopolymers connected by flexible linkers

Networks of the biopolymer actin, cross-linked by the compliant protein filamin, form soft gels. They can, however, withstand large shear stresses due to their pronounced nonlinear elastic behavior. The nonlinear elasticity can be controlled by varying the number of cross-links per actin filament. We propose and test a model of rigid filaments decorated by multiple flexible linkers that is in quantitative agreement with experiment. This allows us to estimate loads on individual cross-links, which we find to be less than 10 pN. © 2009 The American Physical Society

The Influence of Social Dependencies on Decision-Making: Initial Investigations with a New Game

This paper describes a new multi-player computer game, Colored Trails (CT), which may be played by people, computers and heterogeneous groups. CT was designed to enable investigation of properties of decision-making strategies in multi-agent situations of varying complexity. The paper presents the results of an initial series of experiments of CT games in which agents' choices affected not only their own outcomes but also the outcomes of other agents. It compares the behavior of people with that of computer agents deploying a variety of decision-making strategies. The results align with behavioral economics studies in showing that people cooperate when they play and that factors of social dependency influence their levels of cooperation. Preliminary results indicate that people design agents to play strategies closer to game-theory predictions, yielding lower utility. Additional experiments show that such agents perform worse than agents designed to make choices that resemble human cooperative behavior. The paper describes challenges raised by these results for designers of agents, especially agents that need to operate in heterogeneous groups that include people.Engineering and Applied Science

On the form of growing strings

Patterns and forms adopted by Nature, such as the shape of living cells, the geometry of shells and the branched structure of plants, are often the result of simple dynamical paradigms. Here we show that a growing self-interacting string attached to a tracking origin, modeled to resemble nascent polypeptides in vivo, develops helical structures which are more pronounced at the growing end. We also show that the dynamic growth ensemble shares several features of an equilibrium ensemble in which the growing end of the polymer is under an effective stretching force. A statistical analysis of native states of proteins shows that the signature of this non-equilibrium phenomenon has been fixed by evolution at the C-terminus, the growing end of a nascent protein. These findings suggest that a generic non-equilibrium growth process might have provided an additional evolutionary advantage for nascent proteins by favoring the preferential selection of helical structures.Comment: 4 pages, 3 figures. Accepted for publication in Phys. Rev. Let

Mechanical Perturbation of Filamin A Immunoglobulin Repeats 20-21 Reveals Potential Non-equilibrium Mechanochemical Partner Binding Function

The actin crosslinking protein filamin A (FLNa) mediates mechanotransduction, a conversion of mechanical forces into cellular biochemical signals to regulate cell growth and survival. To provide more quantitative insight into this process, we report results using magnetic tweezers that relate mechanical force to conformational changes of FLNa immunoglobulin-like repeats (IgFLNa) 20–21, previously identified as a mechanosensing domain. We determined the force magnitudes required to unfold previously identified structural organizations of the β-strands in the two domains: IgFLNa 20 unfolds at ~15 pN and IgFLNa 21 unfolding requires significantly larger forces. Unfolded domain IgFLNa 20 can exist in two different conformational states, which lead to different refolding kinetics of the IgFLNa 20 and imply a significant impact on the reformation of the domain pair at reduced force values. We discuss the relevance of the findings to force bearing and mechanosensing functions of FLNa

Elasticity of Semiflexible Biopolymer Networks

We develop a model for gels and entangled solutions of semiflexible biopolymers such as F-actin. Such networks play a crucial structural role in the cytoskeleton of cells. We show that the rheologic properties of these networks can result from nonclassical rubber elasticity. This model can explain a number of elastic properties of such networks {\em in vitro}, including the concentration dependence of the storage modulus and yield strain.Comment: Uses RevTeX, full postscript with figures available at http://www.umich.edu/~fcm/preprints/agel/agel.htm

Dynamic Phase Transitions in Cell Spreading

We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous (a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continous to contractile spreading. We propose that the classification of cell spreading into phases with distinct functional characteristics and protein activity patterns serves as a paradigm for a general program of a phase classification of cellular phenotype. Biological variability is drastically reduced when only the corresponding phases are used for comparison across species/different cell lines.Comment: 4 pages, 5 figure

An Analysis of Prosthodontic Research Productivity: Geographic, Economic, and Collaborative Perspective

Purpose: This study evaluated the quantity of prosthodontic literature produced globally by continent in three prosthodontic journals over a 10‐year period, 1998–2008. Prosthodontic research productivity relative to economic status of countries and collaboration among countries grouped by economic status was assessed. Materials and Methods: Three peer‐reviewed prosthodontic journals were used for the analysis of articles published in 1998, 2003, and 2008: The Journal of Prosthetic Dentistry, International Journal of Prosthodontics , and Journal of Prosthodontics . The country of every author listed for each included article was recorded. The number of articles published by each continent and each country was reported. Countries were grouped according to the World Bank economic classification system, and the number of articles published by each economic class was found. Results: The majority of publications over the 10‐year period were produced in Asia (Japan), Europe (Germany), and North America (USA). Productivity declined by 14.4% in high‐income countries while it increased in upper middle‐, lower middle‐, and low‐income countries. The majority of publications written by upper and lower middle‐ and low‐income countries were independent works. Articles resulting from collaboration increased over time for all economic classes of countries. Conclusions: The origins of prosthodontic literature are becoming more geographically and economically diverse, with increased contributions from Africa, Asia, and South America, and middle‐ and low‐income countries between 1998 and 2008. Collaboration between high‐income countries and the other economic group countries increased over time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90374/1/j.1532-849X.2011.00776.x.pd

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach