Motility-driven glass and jamming transitions in biological tissues

Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. To make quantitative predictions about glass transitions in tissues, we study a self-propelled Voronoi (SPV) model that simultaneously captures polarized cell motility and multi-body cell-cell interactions in a confluent tissue, where there are no gaps between cells. We demonstrate that the model exhibits a jamming transition from a solid-like state to a fluid-like state that is controlled by three parameters: the single-cell motile speed, the persistence time of single-cell tracks, and a target shape index that characterizes the competition between cell-cell adhesion and cortical tension. In contrast to traditional particulate glasses, we are able to identify an experimentally accessible structural order parameter that specifies the entire jamming surface as a function of model parameters. We demonstrate that a continuum Soft Glassy Rheology model precisely captures this transition in the limit of small persistence times, and explain how it fails in the limit of large persistence times. These results provide a framework for understanding the collective solid-to-liquid transitions that have been observed in embryonic development and cancer progression, which may be associated with Epithelial-to-Mesenchymal transition in these tissues.Comment: accepted for publication in Physical Review X, 201

Correlating Cell Shape and Cellular Stress in Motile Confluent Tissues

Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a Self-Propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatio-temporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes. We additionally use stress information to characterize the rheological properties of the tissue. We identify a motility-induced swim stress that adds to the interaction stress to determine the global contractility or extensibility of epithelia. We further show that the temporal correlation of the interaction shear stress determines an effective viscosity of the tissue that diverges at the liquid-solid transition, suggesting the possibility of extracting rheological information directly from traction data.Comment: 12 pages, 9 figure

2010-2011 Collaborative Spotlight: Duo Pianists Leonard and Shen

The Romantic American: An Affair with Dance This has been made possible by the National Endowment for the Arts as part of American Masterpieces: Three Centuries of Artistic Genius.https://spiral.lynn.edu/conservatory_otherseasonalconcerts/1016/thumbnail.jp

Melanocortin 1 receptor targeted imaging of melanoma with gold nanocages and positron emission tomography

Purpose: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. Method: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. Results: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. Conclusion: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics. </jats:sec

Comparative vector competence of North American Lyme disease vectors

Background Understanding the drivers of Lyme disease incidence at broad spatial scales is critical for predicting and mitigating human disease risk. Previous studies have identified vector phenology and behavior, host community composition, and landscape features as drivers of variable Lyme disease risk. However, while the Lyme disease transmission cycles in the eastern and western USA involve different vector species (Ixodes scapularis and Ixodes pacificus, respectively), the role of vector-specific differences in transmission efficiency has not been directly examined. By comparing the performance of traits involved in vector competence between these two species, this study aims to identify how vector competence contributes to variable Lyme disease risk. Methods We used a suite of laboratory experiments to compare the performance of traits related to vector competence for the two USA Lyme disease vectors. For each species, we measured the rate of attachment to a common rodent host, the engorgement weight, and the efficiency of pathogen acquisition (host to tick) and pathogen transmission (tick to host) from laboratory mice. In measuring pathogen acquisition and transmission, we used two different pathogen strains, one sympatric with I. scapularis and one sympatric with I. pacificus, to assess the importance of vector-pathogen coevolutionary history in transmission dynamics. Results We found I. pacificus had significantly higher host attachment success and engorgement weights, but significantly lower pathogen transmission efficiency relative to I. scapularis. Molting success and pathogen acquisition did not differ between these two species. However, pathogen acquisition efficiency was significantly higher for both sympatric vector and pathogen strains than the allopatric pairings. Conclusions This study identified species-specific vector traits as a potential driver of broad scale variation in Lyme disease risk in the USA. In particular, the exceedingly low rates of pathogen transmission from tick to host observed for I. pacificus may limit Lyme disease transmission efficiency in the western USA. Further, observed variation in pathogen acquisition between sympatric and allopatric vector-pathogen strains indicate that vector-pathogen coevolutionary history may play a key role in transmission dynamics. These findings underscore the need to consider vector traits and vector-pathogen coevolution as important factors governing regional Lyme disease risk