Collective cell motility in 3-dimensions: dynamics, adhesions, and emergence of heterogeneity

Collective cell migration is ubiquitous in biology, from development to cancer; it is influenced by heterogeneous cell types, signals and matrix properties, and requires large scale regulation in space and time. Understanding how cells achieve organized collective motility is crucial to addressing cellular and tissue function and disease progression. While current two-dimensional model systems recapitulate the dynamic properties of collective cell migration, quantitative three-dimensional equivalent model systems have proved elusive. The overarching hypothesis of this work is that cell collectives are heterogeneous in nature; and that the influence of biochemical, physical, and mechanical factors combined leads to diverse physical behaviors. The central goal of this work is to establish standard tools for the understanding of 3D collective cell motility by treating individual cell-collectives as independent entities. An experimental model studies cell collectives by tracking individual cells within cell cohorts embedded in three dimensional collagen scaffolding. A computational model of 3-dimensional multi-scale self-propelled particles recreates experimental data and accounts for intercellular adhesion dynamics. A custom algorithm identifies cellular cohorts from experimental and simulated data so these may be treated as independent entities. A second custom algorithm quantifies the temporal and spatial heterogeneity of motion in cell cohorts during ‘motility events’ observed in experiments and simulations. The results show that cell-cohorts in 3D are dynamic with spatial and temporal heterogeneity; cohesive motility events can emerge without an external driving agent. Simulated cohorts are able to recreate experimental motility event signatures. Together these model systems and analytical techniques are some of the first to address collective motility of adhesive cellular cohorts in 3-dimensions

Nanomechanics of Multiple Units in the Erythrocyte Membrane Skeletal Network

Erythrocytes undergo deformations when they transport O(2) and CO(2) across the membrane, yet the 3D nanomechanics of the skeletal network remains poorly understood. Expanding from our previous single isolated unit, we now simulate networks consisting of 1–10 concentric rings of repeating units in equibiaxial deformation. The networks are organized with (1) a 3D model for a single unit, (2) a wrap-around mode between Sp and actin protofilament in the intra-unit interaction, and (3) a random inter-unit connectivity. These assumptions permit efficient five-degrees-of-freedom (5DOF) simulations when up to 30 pN of radial forces are applied to the boundary spectrin (Sp) and the center and other units are analyzed. As 6 Sp balance their tensions, hexagonal units become irregular. While actin protofilaments remain tangent to the network, their yaw (Φ) angles change drastically with addition of neighboring units or an Sp unfolding. It is anticipated that during deformation, transmembrane complexes associated with the network move laterally through the lipid bilayer and increase the diffusion of molecules across the membrane. When protofilament/Sp sweeps under the lipid bilayer, they mix up the submembrane concentration gradient. Thus, the nanomechanics of actin protofilaments and Sp may enhance the transport of molecules during erythrocyte deformation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10439-010-0040-4) contains supplementary material, which is available to authorized users

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Tumor Treatments Using Certain Drug Therapies: Mathematical Modelling

In this paper, we construct a mathematical model describing immune response to the growth of breast cancer cells and investigate the impact of immunotherapy, chemotherapy and biochemotherapy treatments. We present a model using coupled ordinary differential equations and are also describing the effect of tumor infiltrating lymphocytes (TIL), Interleukin-2 (IL-2) & Interferon alpha (INF- ) on dynamics of tumor cells under the influence of immunotherapy, chemotherapy & biochemotherapy. A new & promising treatment option biochemotherapy has the potential to help reduce the deaths caused by breast cancer. This model is used to evaluate the effects of pulsed application of the drugs. Numerical simulation for some cases show that efficiency of these therapies depends on both variation of tumor size & variation of parameters among two patients. The biochemotherapy more effective than other therapies. Keywords: Immunotherapy, Chemotherapy, Biochemotherapy, Tumor Infg lymphocytes (TIL), Interleukin-2 (IL-2) Interferon-alpha (INF- )

Intramammary schwannoma: a palpable breast mass

Schwannomas are benign tumors arising from the peripheral nerve sheath, commonly occurring in the head, neck, and extensor surfaces of the extremities. They can be associated with neurofibromatosis type II. Our case describes a 48-year-old woman with a 2-week history of a left-sided palpable breast mass. She was referred to radiology, where additional imaging revealed a 1.1-cm mass. A biopsy was performed; histology revealed an intramammary schwannoma. Mammography findings include a well-defined mass without calcification. Ultrasound images have shown hypoechoic, encapsulated, and well-defined lesions without calcification. Histologically, schwannomas reveal alternating Antoni A and Antoni B cellular areas. Schwannomas are also S100-positive on immunohistochemistry. This case is best categorized as a BI-RADS 4A lesions. This case report highlights the importance of both imaging and pathology in the diagnosis of breast neoplasms. Although breast schwannomas are not a common entity, they are an important consideration when evaluating a breast mass

Intramammary schwannoma: a palpable breast mass

Schwannomas are benign tumors arising from the peripheral nerve sheath, commonly occurring in the head, neck, and extensor surfaces of the extremities. They can be associated with neurofibromatosis type II. Our case describes a 48-year-old woman with a 2-week history of a left-sided palpable breast mass. She was referred to radiology, where additional imaging revealed a 1.1-cm mass. A biopsy was performed; histology revealed an intramammary schwannoma. Mammography findings include a well-defined mass without calcification. Ultrasound images have shown hypoechoic, encapsulated, and well-defined lesions without calcification. Histologically, schwannomas reveal alternating Antoni A and Antoni B cellular areas. Schwannomas are also S100-positive on immunohistochemistry. This case is best categorized as a BI-RADS 4A lesions. This case report highlights the importance of both imaging and pathology in the diagnosis of breast neoplasms. Although breast schwannomas are not a common entity, they are an important consideration when evaluating a breast mass