We propose and examine a three filament model of skeletal muscle force generation, thereby extending classical cross-bridge models by involving titin-actin interaction upon active force production. In regions with optimal actin-myosin overlap, the model does not alter energy and force predictions of cross-bridge models for isometric contractions. However, in contrast to cross-bridge models, the three filament model accurately predicts history-dependent force generation in half sarcomeres for eccentric and concentric contractions, and predicts the activation-dependent forces for stretches beyond actin-myosin filament overlap.

Abstract. We consider a class of infinite delay equations in Banach spaces that models arising in the theory of viscoelasticity, for instance. The equation involves a completely monotone convolution kernel with a singularity at t = 0 and a sectorial linear spatial operator. Our main goal here is the construction of a semigroup formulation for the integral equation; in the last part of the paper, we illustrate the potentiality of the approach by considering a stochastic perturbation of the problem. Existence and uniqueness of a weak solution is established. The corresponding evolutionary solution process is Markovian, and the tools of linear analytic semigroup theory can be utilized.Mathematics Subject Classification. 60H15, 60H20, 45K05.

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We examine the stochastic parabolic integral equation of convolution typewhere, is nonnegative and admits a bounded H ∞ -calculus on L q (O; R). The kernels are powers of t,We show that, in the maximal regularity case, whereone has the estimate, where c is independent of G.Here D η t denotes fractional integration if η ∈ (−1, 0), and fractional differentiation if η ∈ (0, 1), both with respect to the t-variable.The proof relies on recent work on stochastic differential equations by v. Neerven, Veraar and Weis, and extends their maximal regularity result to the integral equation case.

Passive forces in sarcomeres are mainly related to the giant protein titin. Titin’s extensible region consists of spring-like elements acting in series. In skeletal muscles these elements are the PEVK segment, two distinct immunoglobulin (Ig) domain regions (proximal and distal), and a N2A portion. While distal Ig domains are thought to form inextensible end filaments in intact sarcomeres, proximal Ig domains unfold in a force- and time-dependent manner. In length-ramp experiments of single titin strands, sequential unfolding of Ig domains leads to a typical saw-tooth pattern in force-elongation curves which can be simulated by Monte Carlo simulations. In sarcomeres, where more than a thousand titin strands are arranged in parallel, numerous Monte Carlo simulations are required to estimate the resultant force of all titin filaments based on the non-uniform titin elongations. To simplify calculations, the stochastic model of passive forces is often replaced by linear or non-linear deterministic and phenomenological functions. However, new theories of muscle contraction are based on the hypothesized binding of titin to the actin filament upon activation, and thereby on a prominent role of the structural properties of titin. Therefore, these theories necessitate a detailed analysis of titin forces in length-ramp experiments. In our study we present a simple and efficient alternative to Monte Carlo simulations. Based on a structural titin model, we calculate the exact probability distributions of unfolded Ig domains under length-ramp conditions needed for rigorous analysis of expected forces, distribution of unfolding forces, etc. Due to the generality of our model, the approach is applicable to a wide range of stochastic protein unfolding problems.

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