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At least 217 records · Page 12Linked to original sources

arXiv2013

Glassy dynamics in three-dimensional embryonic tissues

Many biological tissues are viscoelastic, behaving as elastic solids on short timescales and fluids on long timescales. This collective mechanical behavior enables and helps to guide pattern formation and tissue layering. Here we investigate the mechanical properties of three-dimensional tissue explants from zebrafish embryos by analyzing individual cell tracks and macroscopic mechanical response. We find that the cell dynamics inside the tissue exhibit features of supercooled fluids, including subdiffusive trajectories and signatures of caging behavior. We develop a minimal, three-parameter mechanical model for these dynamics, which we calibrate using only information about cell tracks. This model generates predictions about the macroscopic bulk response of the tissue (with no fit parameters) that are verified experimentally, providing a strong validation of the model. The best-fit model parameters indicate that although the tissue is fluid-like, it is close to a glass transition, suggesting that small changes to single-cell parameters could generate a significant change in the viscoelastic properties of the tissue. These results provide a robust framework for quantifying and modeling mechanically-driven pattern formation in tissues.

cond-mat.soft↗

arXiv2013

Realizing Bone-mass Generation Through a Density Type Theoretical Archetype

The dynamic process of the formation of bone-mass in case of humans is studied to gather precise understanding about the same with the motivation of applying these concepts for healing of bone-fracture and non-unions in non-invasive manner. Three cellular ingredients, osteoblasts, osteoclasts and osteocytes are predominant players in generating new bone-mass in which a host of hormones, proteins and minerals have potential supportive role. Considering population density of these three biological cells osteoblasts, osteoclasts and osteocytes as variables, we formulate a theoretical model, in the form of a set of time differential equations in order to emulate the dynamic process of bone-mass creation. High relative abundance of osteocytes at asymptotic scale together with moderate level values of osteoblasts and osteoclasts cell populations signifies formation of bone-matter in our theoretical archetype. The archetype has been studied through both analytical and numerical channels, significant results are emphasized and relevant conclusions are drawn. Certain predictive statements are also made which could be put to future in-vivo clinical test or in-vitro physiological experimentation as well.

q-bio.TO↗

arXiv2013

Order, intermittency and pressure fluctuations in a system of proliferating rods

Non-motile elongated bacteria confined in two-dimensional open micro-channels can exhibit collective motion and form dense monolayers with nematic order if the cells proliferate, i.e., grow and divide. Using soft molecular dynamics simulations of a system of rods interacting through short range mechanical forces, we study the effects of the cell growth rate, the cell aspect ratio and of the sliding friction on nematic ordering and on pressure fluctuations in confined environments. Our results indicate that rods with aspect ratio >3.0 reach quasi-perfect nematic states at low sliding friction. At higher frictions, the global nematic order parameter shows intermittent fluctuations due to sudden losses of order and the time intervals between these bursts are power-law distributed. The pressure transverse to the channel axis can vary abruptly in time and shows hysteresis due to lateral crowding effects. The longitudinal pressure field is on average correlated to nematic order, but it is locally very heterogeneous and its distribution follows an inverse power-law, in sharp contrast with non-active granular systems. We discuss some implications of these findings for tissue growth.

cond-mat.soft↗

arXiv2013

A Measure of Control for Secondary Cytokine-Induced Injury of Articular Cartilage: A Computational Study

In previous works, the author and collaborators establish a mathematical model for injury response in articular cartilage. In this paper we use mathematical software and computational techniques, applied to an existing model to explore in more detail how the behavior of cartilage cells is influenced by several of, what are believed to be, the most significant mechanisms underlying cartilage injury response at the cellular level. We introduce a control parameter, the radius of attenuation, and present some new simulations that shed light on how inflammation associated with cartilage injuries impacts the metabolic activity of cartilage cells. The details presented in the work can help to elucidate targets for more effective therapies in the preventative treatment of post-traumatic osteoarthritis.

q-bio.QM↗

arXiv2013

The Cancer Diaspora: Metastasis beyond the seed and soil hypothesis

Do cancer cells escape their confinement of their original habitat in the primary tumor or are they forced out by ecological changes in their home niche? Describing metastasis in terms of a simple one-way migration of cells from the primary to target organs is an insufficient concept to cover the nuances of cancer spread. A diaspora is the scattering of people away from an established homeland. To date, diaspora has been a uniquely human term utilized by social scientists, however, the application of the diaspora concept to metastasis may yield new biological insights as well as therapeutic paradigms. The diaspora paradigm takes into account and models several variables: the quality of the primary tumor microenvironment, the fitness of individual cancer cell migrants as well as migrant populations, the rate of bidirectional migration of cancer and host cells between cancer sites, and the quality of the target microenvironments to establish metastatic sites. Ecological scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies. For example, ecological traps, habitats that lead to the extinction of a species, can be developed to attract cancer cells to a place where they can be better exposed to treatments or to cells of the immune system for improved antigen presentation. Merging the social science concept of diaspora with ecological and population sciences concepts can inform the cancer field to understand the biology of tumorigenesis and metastasis and inspire new ideas for therapy.

q-bio.TO↗

arXiv2013

The Control of Branching Morphogenesis

Many organs of higher organisms are heavily branched structures and arise by an at first sight similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and in how far physical and geometric constraints determine the branching process. Here we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts.

q-bio.TO↗

arXiv2013

Reduction of breast cancer relapses with perioperative non-steroidal anti-inflammatory drugs: new findings and a review

To explain a bimodal pattern of hazard of relapse among early stage breast cancer patients identified in multiple databases, we proposed that late relapses result from steady stochastic progressions from single dormant malignant cells to avascular micrometastases and then on to growing deposits. However in order to explain early relapses, we had to postulate that something happens at about the time of surgery to provoke sudden exits from dormant phases to active growth and then to detection. Most relapses in breast cancer are in the early category. Recent data from Forget et al suggests an unexpected mechanism. They retrospectively studied results from 327 consecutive breast cancer patients comparing various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Relapse hazard updated Sept 2011 are presented. A common Non-Steroidal Anti-Inflammatory Drug (NSAID) analgesic used in surgery produced far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. Transient systemic inflammation accompanying surgery could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent.

q-bio.TO↗

arXiv2013

Determining equilibrium osmolarity in Poly(ethylene glycol) / Chondrotin sulfate gels mimicking articular cartilage

We present an experimentally guided, multi-phase, multi-species polyelectrolyte gel model to make quantitative predictions on the electro-chemical properties of articular cartilage. The mixture theory consists of two different types of polymers: Poly(ethylene gylcol) (PEG), Chondrotin sulfate (ChS), water (acting as solvent) and several different ions: H$^+$, Na$^+$, Cl$^-$. The polymer chains have covalent cross-links modeled using Doi rubber elasticity theory. Numerical studies on polymer volume fraction and net osmolarity (difference in the solute concentration across the gel) show the interplay between ionic bath concentrations, pH, polymer mass in the solvent and the average charge per monomer; governing the equilibrium swelled / de-swelled state of the gel. We conclude that swelling is aided due to a higher average charge per monomer (or a higher percentage of charged ChS component of the polymer), low solute concentration in the bath, a high pH or a low cross-link fraction. However, the swelling-deswelling transitions could be continuous or discontinuous depending upon the relative influence of the various competing forces.

q-bio.TO↗

arXiv2013

Multifocality and recurrence risk: a quantitative model of field cancerization

Primary tumors often emerge within genetically altered fields of premalignant cells that appear histologically normal but have a high chance of progression to malignancy. Clinical observations have suggested that these premalignant fields pose high risks for emergence of secondary recurrent tumors if left behind after surgical removal of the primary tumor. In this work, we develop a spatio-temporal stochastic model of epithelial carcinogenesis, combining cellular reproduction and death dynamics with a general framework for multi-stage genetic progression to cancer. Using this model, we investigate how macroscopic features (e.g. size and geometry of premalignant fields) depend on microscopic cellular properties of the tissue (e.g.\ tissue renewal rate, mutation rate, selection advantages conferred by genetic events leading to cancer, etc). We develop methods to characterize how clinically relevant quantities such as waiting time until emergence of second field tumors and recurrence risk after tumor resection. We also study the clonal relatedness of recurrent tumors to primary tumors, and analyze how these phenomena depend upon specific characteristics of the tissue and cancer type. This study contributes to a growing literature seeking to obtain a quantitative understanding of the spatial dynamics in cancer initiation.

q-bio.PE↗

arXiv2013

Simulating Organogenesis in COMSOL: Parameter Optimization for PDE-based models

Morphogenesis is a tightly regulated process that has been studied for decades. We are developing data-based and image-basd mechanistic models for a range of developmental processes with a view to integrate the available knowledge and to better understand the underlying regulatory logic. In our previous papers on simulating organogenesis with COMSOL (German et al COMSOL Conf Procedings 2011; Menshykau and Iber, COMSOL Conf Proceedings 2012) we discussed methods to efficiently solve such models on static and growing domains. A further challenge in modeling morphogenesis is the parameterization of such models. Here we discuss COMSOL-based methods for parameter optimization. These routines can be used to determine parameter sets, for which the simulations reproduce experimental data and constraints. Such data is often image based, but may also come from classical biochemical or genetic experiments.

q-bio.QM↗

arXiv2013

Measurement of acoustic and anatomic changes in oral and maxillofacial surgery patients

We describe an arrangement for simultaneous recording of speech and geometry of vocal tract in patients undergoing surgery involving this area. Experimental design is considered from an articulatory phonetic point of view. The speech and noise signals are recorded with an acoustic-electrical arrangement. The vocal tract is simultaneously imaged with MRI. A MATLAB-based system controls the timing of speech recording and MR image acquisition. The speech signals are cleaned from acoustic MRI noise by a non-linear signal processing algorithm. Finally, a vowel data set from pilot experiments is compared with validation data from anechoic chamber as well as with Helmholtz resonances of the vocal tract volume.

physics.med-ph↗

arXiv2013

High Throughput Screening of Natural Phenolic Compounds Against Migration of Metastatic Triple-Negative Breast Cancer (TNBC) Cells

In this report, we hypothesize that natural phenolic compounds may present a new class of chemotherapeutics against migration of metastatic triple-negative breast cancers (TNBC). In this project we will screen a small library of phenolic compounds to test this hypothesis, identify compounds that show efficacy against TNBC cell migration, and elucidate underlying molecular mechanisms.

q-bio.CB↗

arXiv2013

Mechanical Therapy as a Potential Green Way to Attack Cancer Disease

Mechanical force is tightly connected to human health status, and the occurrence of disease can generally be ascribed to certain loss of force balance. However, the role of mechanical approaches in tumor therapy is largely neglected, while the currently available cancer prevention and treatment methods are generally either expensive or just cause too much side effect. In this article, we present a systematic interpretation on a promising strategy which was termed here as Mechanical Therapy for the first time based on the fact that mechanical force closely accompanies the whole life (growth and death) of a cell, and plays a crucial role in biological functions. In order to mold the mechanical force as a practical tool for cancer therapy, we expound the effects of the mechanical force related to the tumors from molecule to tissue level and evaluate its feasibility for treatment purpose. It can be conceived that given enough investigations, the mechanical therapy may generate big potential to open new windows for cancer prevention, relieving or even destroying if well administrated. As an easy going and convenient method, a systematic and thorough study of mechanical therapy may clarify more options for future clinical practices. Besides, when patients encounter various forces in daily life, they can at least identify the good or bad forces for a better and healthy life style based on the mechanisms thus disclosed.

physics.med-ph↗

arXiv2013

A filter-flow perspective of hematogenous metastasis offers a non-genetic paradigm for personalized cancer therapy

Research into mechanisms of hematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of `seed-soil' relationships. Preceeding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs). We utilize a `filter-flow' paradigm to show that assumptions about CTC dynamics strongly affect metastatic efficiency: without data on CTC dynamics, any attempt to predict metastatic spread in individual patients is impossible.

q-bio.TO↗

arXiv2013

Precision and reproducibility of macroscopic developmental patterns

Developmental processes in multicellular organisms occur far from equilibrium, yet produce complex patterns with astonishing reproducibility. We measure the precision and reproducibility of bilaterally symmetric fly wings across the natural range of genetic and environmental conditions and find that wing patterns are specified with identical spatial precision and are reproducible to within a single cell width. The early fly embryo operates at a similar degree of reproducibility, suggesting that the overall spatial precision of morphogenesis in Drosophila performs at the single cell level, arguably the physical limit of what a biological system can achieve.

q-bio.TO↗

arXiv2013

Simulating Organogenesis in COMSOL: Cell-based Signaling Models

Most models of biological pattern formation are simulated on continuous domains even though cells are discrete objects that provide internal boundaries to the diffusion of regulatory components. In our previous papers on simulating organogenesis in COMSOL (Germann et al COMSOL Conf Procedings 2011; Menshykau and Iber, COMSOL Conf Proceedings 2012) we discussed methods to efficiently solve signaling models on static and growing continuous domains. Here we discuss COMSOL-based methods to study spatio-temporal signaling models at cellular resolution with subcellular compartments, i.e. cell membrane, cytoplasm, and nucleus.

q-bio.QM↗

arXiv2013

A mathematical model of systemic inhibition of angiogenesis in metastatic development

We present a mathematical model describing the time development of a population of tumors subject to mutual angiogenic inhibitory signaling. Based on biophysical derivations, it describes organism-scale population dynamics under the influence of three processes: birth (dissemination of secondary tumors), growth and inhibition (through angiogenesis). The resulting model is a nonlinear partial differential transport equation with nonlocal boundary condition. The nonlinearity stands in the velocity through a nonlocal quantity of the model (the total metastatic volume). The asymptotic behavior of the model is numerically investigated and reveals interesting dynamics ranging from convergence to a steady state to bounded non-periodic or periodic behaviors, possibly with complex repeated patterns. Numerical simulations are performed with the intent to theoretically study the relative impact of potentiation or impairment of each process of the birth/growth/inhibition balance. Biological insights on possible implications for the phenomenon of "cancer without disease" are also discussed.

math.AP↗

arXiv2014

Modeling and simulation of a low grade urinary bladder carcinoma

In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes involved in tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of Cellular Automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on two most common types: bladder polyps and carcinoma {\it in situ}. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment and we expect our model to be a valuable tool in the prediction of tumor grade and progression patterns, based on the exposure to carcinogens and an oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with {\it in vivo} results reported in the corresponding medical literature.

q-bio.QM↗