Colin Paul

National Cancer Institute (USA), National Institutes of Health | NCI · Laborratory of Cell Biology

Biophysical profiling of primary tumors has revealed that individual tumor cells fall along a highly heterogeneous continuum of mechanical phenotypes. One idea is that a subset of tumor cells is “softer” to facilitate detachment and escape from the primary site, a step required to initiate metastasis. However, it has also been postulated that cells...

Cells respond to physical stimuli, such as stiffness¹, fluid shear stress² and hydraulic pressure3,4. Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer⁵. However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity ar...

Tumor cells encounter a myriad of physical cues upon arrest and extravasation in capillary beds. Here, we examined the role of physical factors in non-random organ colonization using a zebrafish xenograft model. We observed a two-step process by which mammalian mammary tumor cells showed non-random organ colonization. Initial homing was driven by v...

Significance Mechanical homeostasis describes how cells sense physical cues from the microenvironment and concomitantly remodel both the cytoskeleton and the surrounding extracellular matrix (ECM). However, the nature of the dynamic coupling between microscale cell and ECM mechanics remains poorly understood. Here we investigate whether cells mecha...

The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast...

Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up app...

The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer and neurodegenerative disorders. Here, we sought a model to interrogate human immune behavior in vivo. We determined that primary human monocytes and macrophages survive in ze...

Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up app...

Sites of metastasis are non-random, with certain types of cancers showing organ preference during distal colonization. Using multiple brain- and bone marrow-seeking human and murine breast cancer subclones, we determined that tumor cells that home to specific murine organs (brain and bone marrow) ultimately colonized analogous tissues (brain and ca...

The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer and neurodegenerative disorders. Here, we sought a model to interrogate human immune behavior in vivo . We determined that primary human monocytes and macrophages survive in z...

Time-lapse, deep-tissue imaging made possible by advances in intravital microscopy has demonstrated the importance of tumour cell migration through confining tracks in vivo. These tracks may either be endogenous features of tissues or be created by tumour or tumour-associated cells. Importantly, migration mechanisms through confining microenvironme...

Time-lapse imaging of biological samples is important for understanding complex (patho)physiological processes. A growing number of point-of-care biomedical assays rely on real-time imaging of flowing or migrating cells. However, the cost and complexity of integrating experimental models simulating physiologically relevant microenvironments with bu...

Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topog...

Obscurins are a family of giant cytoskeletal proteins, originally identified in striated muscles where they have structural and regulatory roles. We recently showed that obscurins are abundantly expressed in normal breast epithelial cells where they play tumor and metastasis suppressing roles, but are nearly lost from advanced stage breast cancer b...

The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues, has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysi...

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunct...

Planar microfluidic platforms for vector chromatography, in which different species fan out in different directions and can be continuously sorted, are particularly promising for the high throughput separation of multicomponent mixtures. We carry out a computational study of the vector separation of dilute suspensions of rigid and flexible particle...

Cells migrate in vivo within three-dimensional (3D) extracellular matrices. Cells also migrate through 3D longitudinal channels formed between the connective tissue and the basement membrane of muscle, nerve, and epithelium. Although traction forces have been measured during 2D cell migration, no assay has been developed to probe forces during migr...

Using a microchannel assay, we demonstrate that cells adopt distinct signaling strategies to modulate cell migration in different physical microenvironments. We studied α4β1 integrin-mediated signaling, which regulates cell migration pertinent to embryonic development, leukocyte trafficking, and melanoma invasion. We show that α4β1 integrin promote...

Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. U...

Supplementary figures 1-6

Cell migration on planar surfaces is driven by cycles of actin protrusion, integrin-mediated adhesion, and myosin-mediated contraction; however, this mechanism may not accurately describe movement in 3-dimensional (3D) space. By subjecting cells to restrictive 3D environments, we demonstrate that physical confinement constitutes a biophysical stimu...

The ABE process has been around for decades to produce butanol. However, yields are typically low. We are exploring a two step process, first proposed by Ramey (1998 patent) to produce butanol. In the second step of thei process, butyric acid is used to produce butanol. Although this has been explored, little has been looked at using pervaporation...

Butanol is a promising alternative fuel, with many properties comparable to those of gasoline. However, butanol production by acetone-butanol-ethanol fermentation is limited by end-product inhibition at low solvent concentrations. Butanol production could be greatly enhanced if fermentation is coupled with product removal. This study focuses on the...

Researchers at Washington State University have developed miniaturized hands-on learning stations or Desktop Learning Modules (DLM) to help demonstrate most basic fluid and heat transfer concepts in the classroom. Low-cost, 1 ft3 modules have been developed with interchangeable cartridges for dye injection into a flow stream; flow measurement with...