Bulletin of the American Physical Society
APS March Meeting 2015
Volume 60, Number 1
Monday–Friday, March 2–6, 2015; San Antonio, Texas
Session G47: Focus Session: Physics of Cancer |
Hide Abstracts |
Sponsoring Units: DBIO Chair: Rachel Lee, University of Maryland Room: 217B |
Tuesday, March 3, 2015 11:15AM - 11:27AM |
G47.00001: ABSTRACT WITHDRAWN |
Tuesday, March 3, 2015 11:27AM - 11:39AM |
G47.00002: Does Tensile Rupture of Tumor Basement Membrane Mark the Onset of Cancer Metastasis? Sai Prakash Recognizing a conceptual analogy from polymer physics and reasoning via induction, we infer the plausibility that a malignant tumor (carcinoma) grows in size until a threshold determined by its mechanochemical state in relation to its microenvironment whence, peripheral cells undergo epithelial-to-mesenchymal transitions (EMT) facilitating metastasis. This state is equated to the tensile yielding/rupture of the proteolytically-weakened basement membrane (BM) that encapsulates the growing neoplasm. BMs are typically constituted of tri-continuous hydrogel networks of collagen-IV, laminin, and interstitial fluid, with connector proteins such as nidogens, and perlecans. We test this postulate by formulating a theoretical model based on continuum fluid-solid mechanics, diffusion, and biochemical kinetics of energy metabolism. Herein, a prototypical, viscous tumor spheroid grows radially, consuming metabolic nutrients while being constrained by an elastic BM \textit{ca.} 0.5-2 microns-thick, and cell adhesion molecules (CAMs), chiefly cadherins and integrins. The model is computationally analyzed via Comsol$^{\mathrm{\mbox{\textregistered }}}$. Results validate the \textit{a priori} conjecture, and predict subsequent crack-tip stresses shifting strains on the CAMs from compressive to tensile, that might also indicate mechanotransduced switches in their conformations, such as from non-invasive, adhesive E-cadherins to invasive, non-adhesive N-cadherin phenotypes. [Preview Abstract] |
Tuesday, March 3, 2015 11:39AM - 11:51AM |
G47.00003: Mechanical properties of growing melanocytic nevi and the progression to melanoma Alessandro Taloni, Alexander Alemi, Emilio Ciusani, James P. Sethna, Stefano Zapperi, Caterina A. M. La Porta Melanocytic nevi are benign proliferations that sometimes turn into malignant melanoma in a way that is still unclear from the biochemical and genetic point of view. Diagnostic and prognostic tools are then mostly based on dermoscopic examination and morphological analysis of histological tissues. To investigate the role of mechanics and geometry in the morpholgical dynamics of melanocytic nevi, we present a computational model for cell proliferation in a layered non-linear elastic tissue. Our simulations show that the morphology of the nevus is correlated to the initial location of the proliferating cell starting the growth process and to the mechanical properties of the tissue. We also demonstrate that melanocytes are subject to compressive stresses that fluctuate widely in the nevus and depend on the growth stage. Numerical simulations of cells in the epidermis releasing matrix metalloproteinases display an accelerated invasion of the dermis by destroying the basal membrane. Moreover, we show experimentally that osmotic stress and collagen inhibit growth in primary melanoma cells while the effect is much weaker in metastatic cells. [Preview Abstract] |
Tuesday, March 3, 2015 11:51AM - 12:03PM |
G47.00004: ABSTRACT WITHDRAWN |
Tuesday, March 3, 2015 12:03PM - 12:15PM |
G47.00005: Reusable Floating-Electrode Sensor for Real-Time Electrophysiological Monitoring of Nonadherent Cells Viet Anh Pham Ba, Van-Thao Ta, Juhun Park, Eun Jin Park, Seunghun Hong We herein report the development of a reusable floating-electrode sensor (FES) based on aligned single-walled carbon nanotubes, which allowed quantitatively monitoring the electrophysiological responses from nonadherent cells. The FES was used to measure the real-time responses of normal lung cells and small-cell lung cancer (SCLC) cells to the addition of nicotine. The SCLC cells exhibited rather large electrophysiological responses to nicotine compared to normal cells, which was attributed to the overexpressed nicotinic acetylcholine receptors (nAChRs) in the SCLC cells. Importantly, using only a single device could measure repeatedly the responses of multiple individual cells to various drugs, enabling statistically meaningful measurements without errors from the device-to-device variations of the sensor characteristics. As results, that the treatment with drugs such as genistin or daidzein reduced Ca$^{2+}$ influx in SCLC cells was found. Moreover, tamoxifen, has been known as an anti-estrogen compound, was found to only partly block the binding of daidzein to nAChRs. Our FES can be a promising tool for various biomedical applications such as drug screening and therapy monitoring. [Preview Abstract] |
Tuesday, March 3, 2015 12:15PM - 12:27PM |
G47.00006: Thermorheology of living cells---impact of temperature variations on cell mechanics Josef Kas, Tobias Kiessling, Anatol Fritsch, Roland Stange Upon temperature changes, we observe a systematic shift of creep compliance curves J(t) for single living breast epithelial cells. We use a dual-beam laser trap (optical stretcher) to induce temperature jumps within milliseconds, while simultaneously measuring the mechanical response of whole cells to optical force. The cellular mechanical response was found to differ between sudden temperature changes compared to slow, long-term changes implying adaptation of cytoskeletal structure. Interpreting optically induced cell deformation as a thermorheological experiment allows us to consistently explain data on the basis of time--temperature superposition, well known from classical polymer physics. Measured time shift factors give access to the activation energy of the viscous flow of MCF-10A breast cells, which was determined to be $\sim$ 80 kJ/mol. The presented measurements highlight the fundamental role that temperature plays for the deformability of cellular matter. We propose thermorheology as a powerful concept to assess the inherent material properties of living cells and to investigate cell regulatory responses upon environmental changes. [Preview Abstract] |
Tuesday, March 3, 2015 12:27PM - 12:39PM |
G47.00007: Optical and Nanoparticle Analysis of Normal and Cancer Cells by Light Transmission Spectroscopy Alison Deatsch, Nan Sun, Jeffery Johnson, Sharon Stack, John Szajko, Christopher Sander, Roland Rebuyon, Judah Easton, Carol Tanner, Steven Ruggiero We have investigated the optical properties of human oral and ovarian cancer and normal cells. Specifically, we have measured the absolute optical extinction for intra-cellular material (lysates) in aqueous suspension. Measurements were conducted over a wavelength range of 250 to 1000 nm with 1 nm resolution using Light Transmission Spectroscopy (LTS). This provides both the absolute extinction of materials under study and, with Mie inversion, the absolute number of particles of a given diameter as a function of diameter in the range of 1 to 3000 nm. Our preliminary studies show significant differences in both the extinction and particle size distributions associated with cancer versus normal cells, which appear to be correlated with differences in the particle size distribution in the range of approximately 50 to 250 nm. Especially significant is a clearly higher density of particles at about 100 nm and smaller for normal cells. [Preview Abstract] |
Tuesday, March 3, 2015 12:39PM - 12:51PM |
G47.00008: Role of differential physical properties in emergent behavior of 3D cell co-cultures Dan Kolbman, Moumita Das The biophysics of binary cell populations is of great interest in many biological processes, whether the formation of embryos or the initiation of tumors [1]. During these processes, cells are surrounded by other cell types with different physical properties, often with important consequences. For example, recent experiments on a co-culture of breast cancer cells and healthy breast epithelial cells suggest that the mechanical mismatch between the two cell types may contribute to enhanced migration of the cancer cells [2]. Here we explore how the differential physical properties of different cell types may influence cell-cell interaction, aggregation, and migration. To this end, we study a proof of concept model-- a three-dimensional binary system of interacting, active, and deformable particles with different physical properties such as elastic stiffness, contractility, and particle-particle adhesion, using Langevin Dynamics simulations. Our results may provide insights into emergent behavior such as segregation and differential migration in cell co-cultures in three dimensions.\\[4pt] [1] S. Suresh, Acta Biomaterialia 3, 413 (2007).\\[0pt] [2] M. H. Lee, P. H. Wu, J. R. Staunton, R. Ros, G. D. Longmore, and D. Wirtz, Biophysical Journal 102, 2731 (2012). [Preview Abstract] |
Tuesday, March 3, 2015 12:51PM - 1:03PM |
G47.00009: Modeling mechanical interactions between cancerous mammary acini Jeffrey Wang, Jan Liphardt, Chris Rycroft The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. \textit{Ex vivo} experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces. [Preview Abstract] |
Tuesday, March 3, 2015 1:03PM - 1:39PM |
G47.00010: Wave-Based Mechanisms for Contact Guidance and Collective Cell Migration Invited Speaker: Wolfgang Losert The migration of cells in streams, and the crossover from collective cell behavior to individual cell migration is one of the key physical steps in cancer metastasis. This migration occurs in the context of a microenvironment with specific mechanics and texture that may guide the metastatic process. Studies on cell lines indicate that an increasing metastatic potential of cells is associated not with changes in migration speed, but with a decrease in collective motion and increasing chaotic movement fields of groups of cells. I will describe how an underlying wave-like process of the cellular scaffolding that drives persistent migration contributes to the ability of cells to move collectively. I will further show that the same internal waves also allow cells to recognize and follow surface nanotopography on scales comparable to these internal waves. This facilitates contact guidance by the texture of their environment. [Preview Abstract] |
Tuesday, March 3, 2015 1:39PM - 1:51PM |
G47.00011: Computational model for chromosomal instabilty Stefano Zapperi, Zsolt Bertalan, Zoe Budrikis, Caterina La Porta Faithful segregation of genetic material during cell division requires alignment of the chromosomes between the spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated into a coherent picture. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compares well with early observations in mammalian cell spindles. Our results shed new light on the origin of several pathological conditions related to chromosomal instability. [Preview Abstract] |
Tuesday, March 3, 2015 1:51PM - 2:03PM |
G47.00012: Computational modeling of the spatiotemporal dynamics of cancer stem cells Alexandra Signoriello, Marcus Bosenberg, Mark Shattuck, Corey O'Hern Cancer stem cells can differentiate into any cell type in a particular tumor, and thus can reform a tumor even when seeded from a single cell. Despite their importance, the identification of stem cells, their interactions, and how and why they malfunction to cause cancer and form tumors are not well understood. We have developed discrete element modeling (DEM) simulations to investigate the role of stem cells in the formation of heterogeneous cell populations in melanoma tumors. The DEM simulations include elastic, excluded volume, and signaling interactions between cells and rates for cell differentiation, apoptosis, and growth. The DEM is calibrated to results from experimental studies of melanoma tumor growth in mouse models. We use the simulations to generate virtual tumors and study their morphology and cell subtype populations as a function of time. [Preview Abstract] |
Tuesday, March 3, 2015 2:03PM - 2:15PM |
G47.00013: Characterization of Collective Cell Migration Dynamics Rachel Lee, Haicen Yue, Wouter-Jan Rappel, Wolfgang Losert During cancer progression, tumor cells invade the surrounding tissue and migrate throughout the body, forming clinically dangerous secondary tumors. This metastatic process begins when cells leave the primary tumor, either as individual cells or collectively migrating groups. Here we present data on the migration dynamics of epithelial sheets composed of many cells. Using quantitative image analysis techniques, we are able to extract motion information from time-lapse images of cell lines with varying malignancy. Adapting metrics originally used to study fluid flows we are able to characterize the migration dynamics of these cell lines. By describing the migration dynamics in great detail, we are able to make a clear comparison of our results to a simulation of collective cell migration. Specifically, we explore whether leader cells are required to describe our expanding sheets of cells and whether the answer depends on individual cell activity. [Preview Abstract] |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700