Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human beta-cardiac myosin
JOURNAL OF EXPERIMENTAL BIOLOGY
2016; 219 (2): 161-167
Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments
2015; 10 (8): 696-700
Sacrificial layer technique for axial force post assay of immature cardiomyocytes
2013; 15 (1): 171-181
The sarcomere of muscle is composed of tens of thousands of myosin motors that self-assemble into thick filaments and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal lattice. Together, these actin-myosin interactions enable large-scale movement and force generation, two primary attributes of muscle. Research on isolated fibres has provided considerable insight into the collective properties of muscle, but how actin-myosin interactions are coordinated in an ensemble remains poorly understood. Here, we show that artificial myosin filaments, engineered using a DNA nanotube scaffold, provide precise control over motor number, type and spacing. Using both dimeric myosin V- and myosin VI-labelled nanotubes, we find that neither myosin density nor spacing has a significant effect on the gliding speed of actin filaments. This observation supports a simple model of myosin ensembles as energy reservoirs that buffer individual stochastic events to bring about smooth, continuous motion. Furthermore, gliding speed increases with cross-bridge compliance, but is limited by Brownian effects. As a first step to reconstituting muscle motility, we demonstrate human β-cardiac myosin-driven gliding of actin filaments on DNA nanotubes.
View details for DOI 10.1038/NNANO.2015.132
View details for Web of Science ID 000359754500014
View details for PubMedID 26149240
Planar patterned stretchable electrode arrays based on flexible printed circuits.
Journal of micromechanics and microengineering : structures, devices, and systems
2013; 23 (10)
Immature primary and stem cell-derived cardiomyocytes provide useful models for fundamental studies of heart development and cardiac disease, and offer potential for patient specific drug testing and differentiation protocols aimed at cardiac grafts. To assess their potential for augmenting heart function, and to gain insight into cardiac growth and disease, tissue engineers must quantify the contractile forces of these single cells. Currently, axial contractile forces of isolated adult heart cells can only be measured by two-point methods such as carbon fiber techniques, which cannot be applied to neonatal and stem cell-derived heart cells because they are more difficult to handle and lack a persistent shape. Here we present a novel axial technique for measuring the contractile forces of isolated immature cardiomyocytes. We overcome cell manipulation and patterning challenges by using a thermoresponsive sacrificial support layer in conjunction with arrays of widely separated elastomeric microposts. Our approach has the potential to be high-throughput, is functionally analogous to current gold-standard axial force assays for adult heart cells, and prescribes elongated cell shapes without protein patterning. Finally, we calibrate these force posts with piezoresistive cantilevers to dramatically reduce measurement error typical for soft polymer-based force assays. We report quantitative measurements of peak contractile forces up to 146 nN with post stiffness standard error (26 nN) far better than that based on geometry and stiffness estimates alone. The addition of sacrificial layers to future 2D and 3D cell culture platforms will enable improved cell placement and the complex suspension of cells across 3D constructs.
View details for DOI 10.1007/s10544-012-9710-3
View details for Web of Science ID 000313517800018
Computational modeling of bone density profiles in response to gait: a subject-specific approach
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
2012; 11 (3-4): 379-390
For stretchable electronics to achieve broad industrial application, they must be reliable to manufacture and must perform robustly while undergoing large deformations. We present a new strategy for creating planar stretchable electronics and demonstrate one such device, a stretchable microelectrode array based on flex circuit technology. Stretchability is achieved through novel, rationally designed perforations that provide islands of low strain and continuous low-strain pathways for conductive traces. This approach enables the device to maintain constant electrical properties and planarity while undergoing applied strains up to 15%. Materials selection is not limited to polyimide composite devices and can potentially be implemented with either soft or hard substrates and can incorporate standard metals or new nano-engineered conductors. By using standard flex circuit technology, our planar microelectrode device achieved constant resistances for strains up to 20% with less than a 4% resistance offset over 120,000 cycles at 10% strain.
View details for DOI 10.1088/0960-1317/23/10/105004
View details for PubMedID 24244075
CRITICAL LOADING DURING SERVE: MODELING STRESS-INDUCED BONE GROWTH IN PERFORMANCE TENNIS PLAYERS
PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE 2008, PTS A AND B
The phenomenon of twisted growth: humeral torsion in dominant arms of high performance tennis players
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING
2009; 12 (1): 83-93
The goal of this study is to explore the potential of computational growth models to predict bone density profiles in the proximal tibia in response to gait-induced loading. From a modeling point of view, we design a finite element-based computational algorithm using the theory of open system thermodynamics. In this algorithm, the biological problem, the balance of mass, is solved locally on the integration point level, while the mechanical problem, the balance of linear momentum, is solved globally on the node point level. Specifically, the local bone mineral density is treated as an internal variable, which is allowed to change in response to mechanical loading. From an experimental point of view, we perform a subject-specific gait analysis to identify the relevant forces during walking using an inverse dynamics approach. These forces are directly applied as loads in the finite element simulation. To validate the model, we take a Dual-Energy X-ray Absorptiometry scan of the subject's right knee from which we create a geometric model of the proximal tibia. For qualitative validation, we compare the computationally predicted density profiles to the bone mineral density extracted from this scan. For quantitative validation, we adopt the region of interest method and determine the density values at fourteen discrete locations using standard and custom-designed image analysis tools. Qualitatively, our two- and three-dimensional density predictions are in excellent agreement with the experimental measurements. Quantitatively, errors are less than 3% for the two-dimensional analysis and less than 10% for the three-dimensional analysis. The proposed approach has the potential to ultimately improve the long-term success of possible treatment options for chronic diseases such as osteoarthritis on a patient-specific basis by accurately addressing the complex interactions between ambulatory loads and tissue changes.
View details for DOI 10.1007/s10237-011-0318-y
View details for Web of Science ID 000300518000008
View details for PubMedID 21604146
Pulsatile pressure system for cellular mechanical stimulation
PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007
This manuscript is driven by the need to understand the fundamental mechanisms that cause twisted bone growth and shoulder pain in high performance tennis players. Our ultimate goal is to predict bone mass density in the humerus through computational analysis. The underlying study spans a unique four level complete analysis consisting of a high-speed video analysis, a musculoskeletal analysis, a finite element based density growth analysis and an X-ray based bone mass density analysis. For high performance tennis players, critical loads are postulated to occur during the serve. From high-speed video analyses, the serve phases of maximum external shoulder rotation and ball impact are identified as most critical loading situations for the humerus. The corresponding posts from the video analysis are reproduced with a musculoskeletal analysis tool to determine muscle attachment points, muscle force vectors and overall forces of relevant muscle groups. Collective representative muscle forces of the deltoid, latissimus dorsi, pectoralis major and triceps are then applied as external loads in a fully 3D finite element analysis. A problem specific nonlinear finite element based density analysis tool is developed to predict functional adaptation over time. The density profiles in response to the identified critical muscle forces during serve are qualitatively compared to X-ray based bone mass density analyses.
View details for DOI 10.1080/10255840802178046
View details for Web of Science ID 000262182900008
View details for PubMedID 18654877