Bulletin of the American Physical Society
APS March Meeting 2015
Volume 60, Number 1
Monday–Friday, March 2–6, 2015; San Antonio, Texas
Session S47: Focus Session: Mechanical Structure-Function Relations in Biological Matter I |
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Sponsoring Units: DBIO Chair: Moumita Das, Rochester Institute of Technology Room: 217B |
Thursday, March 5, 2015 8:00AM - 8:12AM |
S47.00001: Time evolution of cell size distributions in dense cell cultures Evgeniy Khain Living cells in a dense system are all in contact with each other. The common assumption is that such cells stop dividing due to a lack of space. Recent experimental observations have shown, however, that cells continue dividing for a while, but other cells in the system must shrink, to allow the newborn cells to grow to a normal size. Due to these ``pressure'' effects, the average cell size dramatically decreases with time, and the dispersion in cell sizes decreases, too. The collective cell behavior becomes even more complex when the system is expanding: cells near the edges are larger and migrate faster, while cells deep inside the colony are smaller and move slower. This exciting experimental data still needs to be described theoretically, incorporating the distribution of cell sizes in the system. We propose a mathematical model for time evolution of cell size distribution both in a closed and open system. The model incorporates cell proliferation, cell growth after division, cell shrinking due to ``pressure'' from other cells, and possible cell detachment from the interface of a growing colony. This research sheds light on physical and biological mechanisms of cell response to a dense environment and on the role of mechanical stresses in determining the distribution of cell sizes in the system. [Preview Abstract] |
Thursday, March 5, 2015 8:12AM - 8:24AM |
S47.00002: Sorting of colors in the retina Erez Ribak, Amichai Labin, Shadi Safuri, Ido Perlman Our image of the world is detected by photoreceptors, lying at the bottom of the nearly-transparent retina. Lateral neural layers for processing the image temporally, spectrally, and spatially come in front the photoreceptors, not behind them. This reverse order is a long-standing puzzle, which we wish to explain. We found out that cone photoreceptors are attached to metabolic Muller cells which span the retina. Cones provide colour vision at day time, and are surrounded by sensitive rods which function at night. We showed by an analytical and a computational method that the M\"{u}ller cells also serve as fibre optics, concentrating green-red light into the cones, while the excessive blue is scattered to the nearby rods. Spatial and spectral laboratory measurements validate that indeed the shapes and refractive index values of the Muller cells and the surrounding retina separate the colours according to the spectral sensitivities of both cones and rods. These results also explain other effects of vision acuity and colour sensitivity. References A M Labin and E N Ribak, Phys Rev Lett 104, 158102 (2010). A M Labin, S K Safuri, E N Ribak and I Perlman, Nature Comm 5, 4319 (2014). A M Labin and E N Ribak, ``Color sorting by retinal waveguides''. Submitted. [Preview Abstract] |
Thursday, March 5, 2015 8:24AM - 8:36AM |
S47.00003: Role of the tranverse arch in stiffness of the human foot Marcelo A. Dias, Dhiraj K. Singh, Mahesh M. Bandi, Madhusudhan Venkadesan, Shreyas Mandre Human ancestors evolved from walking, around 6 million years (Ma) ago, to regular endurance running, around 2 Ma ago. Simultaneously, the feet evolved from a relatively flat structure like that of current day Chimpanzees (or our hands), to the modern human foot with two arches, a longitudinal and a transversal arch. The feet play a crucial role in locomotion by providing sufficient stiffness for propulsion, and being soft and pliable to absorb impacts and store energy elastically. Here we show that the transverse arch could play a central role in stiffness modulation. We first treat the foot as an elastic shell that is with intrinsic curvature. Calculations, numerics and physical experiments all show that for a foot-like shell, the stiffness has a power-law dependence on transverse curvature beyond a critical value. On the other hand, for purely longitudinally curved feet, or transverse curvature below the critical value, lead to low stiffness like a flat plate. Discrete realizations of a continuum shell, more closely resembling the human foot, also exhibit curvature induced stiffening. These results shed light on the role of the quintessentially human feature of a doubly arched foot, and suggest mechanical consequences of disorders such as a collapsed arch. [Preview Abstract] |
Thursday, March 5, 2015 8:36AM - 8:48AM |
S47.00004: Correlating Viscoelasticity with Metabolism in Single Cells using Atomic Force Microscopy Matthew Caporizzo, Charles Roco, Carme Coll-Ferrer, David Eckmann, Russell Composto Variable indentation-rate rheometric analysis by Laplace transform (VIRRAL), is developed to evaluate Dex-Gel drug carriers as biocompatible delivery agents. VIRRAL provides a general platform for the rapid characterization of the health of single cells by viscoelasticity to promote the self-consistent comparison between cells paramount to the development of early diagnosis and treatment of disease. By modelling the frequency dependence of elastic modulus, VIRRAL provides three metrics of cytoplasmic viscoelasticity: low frequency stiffness, high frequency stiffness, and a relaxation time. THP-1 cells are found to exhibit a frequency dependent elastic modulus consistent with the standard linear solid model of viscoelasticity. VIRRAL indicates that dextran-lysozyme drug carriers are biocompatible and deliver concentrated toxic material (rhodamine or silver nanoparticles) to the cytoplasm of THP-1 cells. The signature of cytotoxicity by rhodamine or silver exposure is a frequency independent 2-fold increase in elastic modulus and cytoplasmic viscosity while the cytoskeletal relaxation time remains unchanged independent of cytoplasmic stiffness. This is consistent with the known toxic mechanism of silver nanoparticles, where mitochondrial injury leads to ATP depletion and metabolic stress causes a decrease of mobility within cytoplasm. [Preview Abstract] |
Thursday, March 5, 2015 8:48AM - 9:00AM |
S47.00005: Linking Mechanics and Statistics in Epidermal Tissues Sangwoo Kim, Sascha Hilgenfeldt Disordered cellular structures, such as foams, polycrystals, or living tissues, can be characterized by quantitative measurements of domain size and topology. In recent work, we showed that correlations between size and topology in 2D systems are sensitive to the shape (eccentricity) of the individual domains: From a local model of neighbor relations, we derived an analytical justification for the famous empirical Lewis law, confirming the theory with experimental data from cucumber epidermal tissue. Here, we go beyond this purely geometrical model and identify mechanical properties of the tissue as the root cause for the domain eccentricity and thus the statistics of tissue structure. The simple model approach is based on the minimization of an interfacial energy functional. Simulations with Surface Evolver show that the domain statistics depend on a single mechanical parameter, while parameter fluctuations from cell to cell play an important role in simultaneously explaining the shape distribution of cells. The simulations are in excellent agreement with experiments and analytical theory, and establish a general link between the mechanical properties of a tissue and its structure. The model is relevant to diagnostic applications in a variety of animal and plant tissues. [Preview Abstract] |
Thursday, March 5, 2015 9:00AM - 9:12AM |
S47.00006: Cell mechanics and immune system link up to fight infections Andrew Ekpenyong, Si Ming Man, Panagiotis Tourlomousis, Sarra Achouri, Eugenia Cammarota, Katherine Hughes, Alessandro Rizzo, Gilbert Ng, Jochen Guck, Clare Bryant Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection. [Preview Abstract] |
Thursday, March 5, 2015 9:12AM - 9:24AM |
S47.00007: Topology optimization of trabecular bone in the human spine Ahmed Elbanna It is widely believed in the realm of biology that the trabecular structure of long bones self-optimizes in response to mechanical loads, in accordance with Wolff's law. Here, we examine this idea by applying techniques from topology optimization the human spine. We consider different domain geometries as well as different load cases to account for the various loading conditions and changes in shape that take place within the spine during day-to-day activities and over the years. We show that the classical approach of minimizing compliance subject to a volume constraint does not yield a sponge-like architecture but results in only vertical trabeculae. Additional constraints/objective functions have to be considered simultaneously. We show that more realistic trabecular geometries may be produced by taking into consideration the function of trabecular bone as a reservoir for minerals and bone marrow production. By maximizing the surface area of the generated voids while minimizing the total volume of the trabeculae subject to a constraint on their buckling strength, we recover the sponge-like structure. Our results shed light on the optimizing conditions for bone structure beyond Wolff's law and provide guidelines for biomimetic material design. [Preview Abstract] |
Thursday, March 5, 2015 9:24AM - 9:36AM |
S47.00008: Structure and Sequence Search on Aptamer-Protein Docking Jiajie Xiao, Keith Bonin, Martin Guthold, Freddie Salsbury Interactions between proteins and deoxyribonucleic acid (DNA) play a significant role in the living systems, especially through gene regulation. However, short nucleic acids sequences (aptamers) with specific binding affinity to specific proteins exhibit clinical potential as therapeutics. Our capillary and gel electrophoresis selection experiments show that specific sequences of aptamers can be selected that bind specific proteins. Computationally, given the experimentally-determined structure and sequence of a thrombin-binding aptamer, we can successfully dock the aptamer onto thrombin in agreement with experimental structures of the complex. In order to further study the conformational flexibility of this thrombin-binding aptamer and to potentially develop a predictive computational model of aptamer-binding, we use GPU-enabled molecular dynamics simulations to both examine the conformational flexibility of the aptamer in the absence of binding to thrombin, and to determine our ability to fold an aptamer. This study should help further de-novo predictions of aptamer sequences by enabling the study of structural and sequence-dependent effects on aptamer-protein docking specificity. [Preview Abstract] |
Thursday, March 5, 2015 9:36AM - 9:48AM |
S47.00009: Non-thermal fluctuations in living cells reveal nonlinear mechanical properties of the cytoskeleton H. Daniel Ou-Yang, Ming-Tzo Wei, Dimitris Vavylonis, Sabrina Jedlicka Living cells are a non-equilibrium mechanical system, largely because intracellular molecular motors consume chemical energy to generate forces that reorganize and maintain cytoskeletal functions. Persistently under tension, the network of cytoskeletal proteins exhibits a nonlinear mechanical behavior where the network stiffness increases with intracellular tension. We examined the nonlinear mechanical properties of living cells by characterizing the differential stiffness of the cytoskeletal network for HeLa cells under different intracellular tensions. Combining active and passive microrheology methods, we measured non-thermal fluctuating forces and found them to be much larger than the thermal fluctuating force. From the variations of differential stiffness caused by the fluctuating non-thermal force for cells under different tension, we obtained a master curve describing the differential stiffness as a function of the intracellular tension. Varying the intracellular tension by treating cells with drugs that alter motor protein activities we found the differential stiffness follows the same master curve that describes intracellular stiffness as a function of intracellular tension. This observation suggests that cells can regulate their mechanical properties by adjusting intracellular tension. [Preview Abstract] |
Thursday, March 5, 2015 9:48AM - 10:24AM |
S47.00010: Geometry, Mechanics, and Microstructure: Relating Structure to Function in Articlar Cartilage Invited Speaker: Jesse Silverberg Climbing cucumbers, popping pollen grains, wrinkled fingers, and curly hair. At heart, the modern revival of mechanics covers a diverse range of biological materials living at the intersection of function and form. It's at this point, where geometry, mechanics and microstructure meet, that we find buckling instabilities, mechanical phase transitions, exotic stress responses, and fracture. While these phenomena are widely observed in many inert materials, we also find them being actively employed in biological tissues, where they have evolved as essential tools for survival. In this talk, I'll specifically address articular cartilage, a biological material that enables smooth and painless joint motion. Using a combination of experimental techniques, an unusual structure-function relationship for this material is empirically determined, and a model based on percolating fiber networks is offered as a solution. In the end, a central theme will emerge placing this tissue in the wider context of ``elastic network materials,'' and a wider need for advanced imaging methods will be called for. [Preview Abstract] |
Thursday, March 5, 2015 10:24AM - 10:36AM |
S47.00011: Effect of Isotropic Assumption on Material Property Reconstructions of the Human Brain using Magnetic Resonance Elastography Aaron Anderson, Curtis Johnson, Joseph Holtrop, Mathew McGarry, Keith Paulsen, Bradley Sutton, Elijah Van Houten, John Georgiadis Neurodegenerative diseases affect the microstructure of the brain and thus have a significant effect on the tissue mechanical properties. In vivo techniques, like magnetic resonance elastography (MRE), have shown promise as a contrast technique for disease detection. MRE is a non-invasive technique for measuring the viscoelastic mechanical properties of biological tissue by applying a low-amplitude shear wave, capturing the wave patterns with specialized magnetic resonance imaging techniques, and employing an isotropic nonlinear inversion (NLI) material property reconstruction. When distinctly different shear wave patterns are applied, NLI reconstructs differences in the real component of the shear modulus of $\sim 2 ~[\mathrm{kPa}]$ within well ordered white matter (WM). The difference is significant due to the human brain only having a range of real shear modulus from $0 ~[\mathrm{kPa}]$ (cerebral spinal fluid) to $\sim 5 ~[\mathrm{kPa}]$ (white matter). The focus of this investigation is to quantify the effect of propagation direction on the reconstructed material properties and examine their relationship to the underlying microstructure in a well ordered, WM regions of the brain (corpus callosum). [Preview Abstract] |
Thursday, March 5, 2015 10:36AM - 10:48AM |
S47.00012: Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage Sarah Kearns, Moumita Das We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings. [Preview Abstract] |
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