Theodore A. Uyeno

What is the role of titin in active muscle

Several properties of muscle defy explanation solely based on the sliding filament-swinging cross-bridge theory. Indeed, muscle behaves as though there is a dynamic “spring” within the sarcomeres. We propose a new “winding filament” mechanism for how titin acts, in conjunction with the cross-bridges, as a force-dependent spring. The addition of titin into active sarcomeres resolves many puzzling muscle characteristics.

A molecular basis for intrinsic muscle properties: implications for motor control.

Motor control comprises not only descending input from the nervous system and proprioceptive feedback, but also muscle viscoelastic properties, body dynamics, and interactions with the environment. Proprioceptive sense organs and spinal reflexes regulate muscle stiffness dynamically during perturbations. In addition to these slower acting reflexes, the nonlinear, viscoelastic behavior of muscles also provides instantaneous dynamic tuning of stiffness during load perturbations. Despite recognition of the contribution of these muscle properties to motor control, a theoretical framework that accounts for them has remained largely undeveloped. We recently proposed a novel molecular mechanism, the “winding filament” hypothesis, which accounts for the viscoelastic properties of active muscle. This hypothesis proposes that the giant, elastic titin protein is first engaged mechanically during Ca2+ activation in skeletal muscle, and the cross-bridges then wind titin on the thin filaments, storing elastic potential energy during force development. Mechanical engagement of the titin spring upon Ca2+ activation provides a mechanism by which nearly invariant contractile and viscoelastic properties can be produced regardless of the initial sarcomere length at which the muscles are activated. Winding of titin on the thin filaments with force development changes a muscle’s equilibrium position and stiffness as a function of muscle recruitment. These changes, in turn, produce forces that move the limbs to their final position regardless of unexpected perturbations. By adjusting their stiffness instantaneously to changes in load, muscles themselves control interactions between body and environment, and manage interactions between antagonistic muscles, which interact via their loads. By providing a biological mechanism for muscle intrinsic properties, the winding filament hypothesis provides inspiration for the design of a new generation of actuators and prostheses that, like muscles, will exhibit self-stabilization based on variable, nonlinear compliance.

Morphology of the muscle articulation joint between the hooks of a flatworm (Kalyptorhynchia, Cheliplana sp.)

Schizorhynch kalyptorhynchs are meiofaunal turbellarian predators that possess an eversible proboscis that can be armed with two stout hooks. The hooks grasp and manipulate prey using a wide range of rotations and translations. These diverse motions are possible because the hook supports may function as a muscle articulation type joint—that is, a joint formed of muscle and connective tissue that connects, separates, and moves the microscopic hooks. We analyze the morphology of the flexible joint in a species of Cheliplana by using three types of microscopy: light, laser scanning confocal, and transmission electron. Radial myofilament bundles are present in the core of the hook supports, and lateral divaricator muscle fibers are located on their lateral surfaces. We develop a novel model for movements of the proboscis and describe the tensile function of the basement membrane that surrounds each hook supports medial glandular region. Contraction of divaricator muscle fibers antagonized by contraction of radial myofilaments causes the lateral bending of the hook supports and opening of the hook apparatus. Relaxation of the divaricator fibers and maximal contraction of the radial myofilaments, which put the medial basement membranes in tension, may cause medial bending in the hook supports and closing of the hook apparatus. During proboscis retraction, closure may also be aided by the compression of the hook apparatus as the proboscis is drawn through the rostral pore. The study provides new insights into the principles of support and movement in muscle articulations.

Effects of activation on the elastic properties of intact soleus muscles with a deletion in titin

ABSTRACT Titin has long been known to contribute to muscle passive tension. Recently, it was also demonstrated that titin-based stiffness increases upon Ca2+ activation of wild-type mouse psoas myofibrils stretched beyond overlap of the thick and thin filaments. In addition, this increase in titin-based stiffness was impaired in single psoas myofibrils from mdm mice, characterized by a deletion in the N2A region of the Ttn gene. Here, we investigated the effects of activation on elastic properties of intact soleus muscles from wild-type and mdm mice to determine whether titin contributes to active muscle stiffness. Using load-clamp experiments, we compared the stress–strain relationships of elastic elements in active and passive muscles during unloading, and quantified the change in stiffness upon activation. Results from wild-type muscles show that upon activation, the elastic modulus increases, elastic elements develop force at 15% shorter lengths, and there was a 2.9-fold increase in the slope of the stress–strain relationship. These results are qualitatively and quantitatively similar to results from single wild-type psoas myofibrils. In contrast, mdm soleus showed no effect of activation on the slope or intercept of the stress–strain relationship, which is consistent with impaired titin activation observed in single mdm psoas myofibrils. Therefore, it is likely that titin plays a role in the increase of active muscle stiffness during rapid unloading. These results are consistent with the idea that, in addition to the thin filaments, titin is activated upon Ca2+ influx in skeletal muscle. Summary: Rapid unloading of intact wild-type and Ttn mutant soleus muscles indicates that titin, an elastic element within muscle sarcomeres, is activated upon Ca2+ influx in skeletal muscle.

Material Properties of Hagfish Skin, with Insights into Knotting Behaviors

Hagfishes (Myxinidae) often integrate whole-body knotting movements with jawless biting motions when reducing large marine carcasses to ingestible items. Adaptations for these behaviors include complex arrangements of axial muscles and flexible, elongate bodies without vertebrae. Between the axial muscles and the hagfish skin is a large, blood-filled subcutaneous sinus devoid of the intricate, myoseptal tendon networks characteristic of the taut skins of other fishes. We propose that the loose-fitting skin of the hagfish facilitates the formation and manipulation of body knots, even if it is of little functional significance to steady swimming. Hagfish skin is a relatively thick, anisotropic, multilayered composite material comprising a superficial, thin, and slimy epidermis, a middle dermal layer densely packed with fibrous tissues, and a deep subdermal layer comprised of adipose tissue. Hagfish skin is stiffer when pulled longitudinally than circumferentially. Stress-strain data from uniaxial tensile tests show that hagfish skins are comparable in tensile strength and stiffness to the taut skins of elongate fishes that do not engage in knotting behaviors (e.g., sea lamprey and penpoint gunnel). Sheath-core-constructed ropes, which serve as more accurate models for hagfish bodies, demonstrate that loose skin (extra sheathing) enhances flexibility of the body (rope). Along with a loose-fitting skin, the morphologies of hagfish skin parallel those of moray eels, which are also known for generating and manipulating figure-eight-style body knots when struggling with prey.

Evolution and Functional Morphology of the Proboscis in Kalyptorhynchia (Platyhelminthes)

Predatory flatworms belonging to the taxon Kalyptorhynchia are characterized by an anterior muscular proboscis that they use to seize prey. In many cases, the proboscis is armed with hooks, derived either from the extracellular matrix that surrounds the muscles or from intracellular deposits in the epithelium covering the proboscis. Glands associated with the proboscis reportedly are venomous; however, there are few direct tests of this hypothesis. This article reviews the structure and current knowledge of the function of the proboscis in the Kalyptorhynchia, points to areas in which the current understanding of phylogenetic relationships within this taxon is incongruent with our hypothesis of how the proboscis evolved, and addresses areas in need of further research, especially as regards functional morphology and biomechanics.

The structure and function of a muscle articulation-type jaw joint of a polychaete worm.

The arrangement of the musculature and the fibers of the extracellular matrix (ECM) in the flexible jaw joint of the sandworm Alitta virens (Annelida, Polychaeta) was studied using dissection and histology. The jaws are capable of a wide range of motions principally related to defense and feeding. The left and right jaws are embedded in and moved by a compact pharyngeal bulb of muscle and ECM that also forms the mouth and esophagus. Eight pharyngeal bulbs were removed and dissected to document gross anatomical features or preserved and embedded in plastic for sectioning in multiple planes. The sections were stained with toluidine blue and basic fuchsin to differentiate muscle and ECM. The sections were then digitized and used to develop a three‐dimensional computer illustration. We hypothesize that the muscle and fibers in the ECM are arranged as a muscular hydrostat to support the movement of the jaws. Four specimens were recorded using a digital video camera and a tank with an angled mirror to record lateral and ventral views of jaw movements during locomotion and biting associated with burrow guarding and feeding. Frame by frame kinematic analysis of this video showed that the jaws move symmetrically in a roughly horizontal plane. Although the angle between the jaws increases and then decreases after maximum gape has been reached, the jaws also translate relative to each other such that the axis of rotation is not fixed. Together, these functional morphological and behavioral data identify the jaw mechanism as a flexible joint known as a muscle articulation. As muscle articulations have been previously described only in the beaks of cephalopods and flatworms, this study implies that this type of joint is more common and important than previously recognized. J. Morphol. 276:403–414, 2015.

Vegetation density estimation in the wild

Remote sensing has revolutionized the efficiency of vegetation mapping, but such techniques remain impractical for mapping some types of flora over relatively limited spatial extents. We propose a deep-learning based framework for automated detection and planar mapping of an epiphytic plant in a forest from geotagged static imagery using inexpensive cameras. Our pipeline consists of two steps: segmentation and spatial distribution estimation. We evaluate several segmentation methods on a novel dataset of roughly 375 outdoor images with per-pixel labels indicating the presence of Spanish moss. We also evaluate the accuracy of the spatial distribution estimates with respect to field measurements by ecologists for Spanish moss.

No support for Heincke's law in hagfish (Myxinidae): lack of an association between body size and the depth of species occurrence

This study tests for interspecific evidence of Heinckes law among hagfishes and advances the field of research on body size and depth of occurrence in fishes by including a phylogenetic correction and by examining depth in four ways: maximum depth, minimum depth, mean depth of recorded specimens and the average of maximum and minimum depths of occurrence. Results yield no evidence for Heinckes law in hagfishes, no phylogenetic signal for the depth at which species occur, but moderate to weak phylogenetic signal for body size, suggesting that phylogeny may play a role in determining body size in this group.