Emergent patterns of collective cell migration under tubular confinement

Xi, Wang; Sonam, Surabhi; Saw, Thuan Beng; Ladoux, Benoît; Lim, Chwee Teck

doi:10.1038/s41467-017-01390-x

Cited by 121 publications

(127 citation statements)

References 66 publications

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“…T‐lymphocytes, which exhibit amoeboid migration mode, also do not lift upward on concave surfaces and have been shown to preferentially migrate in concave areas on a sinusoidal wave substrate (wavelength sinusoid 20–160 µm, amplitude 10 µm) . Xi et al demonstrated that epithelial Madin–Darby canine kidney cells (MDCK) can collectively migrate into concave microtubes ( d = 25–250 µm) and form tubular epithelial cell sheets inside the tubes . Maechler et al recently cultured other epithelial cell lines, MDCK and J3B1A, in concave tubes ( d = 269 ± 13 µm or 428 ± 24 µm).…”

Section: Resultsmentioning

confidence: 99%

Cell‐Perceived Substrate Curvature Dynamically Coordinates the Direction, Speed, and Persistence of Stromal Cell Migration

et al. 2019

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Adherent cells residing within tissues or biomaterials are presented with 3D geometrical cues from their environment, often in the form of local surface curvatures. While there is growing evidence that cellular decision‐making is influenced by substrate curvature, the effect of physiologically relevant, cell‐scale anisotropic curvatures remains poorly understood. This study systematically explores the migration behavior of human bone marrow stromal cells (hBMSCs) on a library of anisotropic curved structures. Analysis of cell trajectories reveals that, on convex cylindrical structures, hBMSC migration speed and persistence are strongly governed by the cellular orientation on the curved structure, while migration on concave cylindrical structures is characterized by fast but non‐aligned and non‐persistent migration. Concurrent presentation of concave and convex substrates on toroidal structures induces migration in the direction where hBMSCs can most effectively avoid cell bending. These distinct migration behaviors are found to be universally explained by the cell‐perceived substrate curvature, which on anisotropic curved structures is dependent on both the temporally varying cell orientation and the 3D cellular morphology. This work demonstrates that cell migration is dynamically guided by the perceived curvature of the underlying substrate, providing an important biomaterial design parameter for instructing cell migration in tissue engineering and regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Cell‐Perceived Substrate Curvature Dynamically Coordinates the Direction, Speed, and Persistence of Stromal Cell Migration

et al. 2019

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“…Alternatively, these epithelioid islands and the budding phenotype on the tumor front may reflect a discrete form of invasion. For example, during renal embryonic development, epithelioid cell clusters collectively migrate during nephric duct elongation, highlighting the migratory potential of epithelioid cells (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

et al. 2018

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Sunitinib is the standard-of-care, first-line treatment for advanced renal cell carcinoma (RCC). Characteristics of treatment-resistant RCC have been described; however, complex tumor adaptation mechanisms obstruct the identification of significant operators in resistance. We hypothesized that resistance is a late manifestation of early, treatment-induced histomolecular alterations; therefore, studying early drug response may identify drivers of resistance. We describe an epithelioid RCC growth pattern in RCC xenografts, which emerges in sunitinib-sensitive tumors and is augmented during resistance. This growth modality is molecularly and morphologically related to the RCC spheroids that advance during in vitro treatment. Based on time-lapse microscopy, mRNA and microRNA screening, and tumor behavior-related characteristics, we propose that the spheroid and adherent RCC growth patterns differentially respond to sunitinib. Gene expression analysis indicated that sunitinib promoted spheroid formation, which provided a selective survival advantage under treatment. Functional studies confirm that E-cadherin is a key contributor to the survival of RCC cells under sunitinib treatment. In summary, we suggest that sunitinib-resistant RCC cells exist in treatment-sensitive tumors and are histologically identifiable.-Lichner, Z., Saleeb, R., Butz, H., Ding, Q., Nofech-Mozes, R., Riad, S., Farag, M., Varkouhi, A. K., dos Santos, C. C., Kapus, A., Yousef, G. M. Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance.

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“…We verify this velocity folding by a simple numerical experiment [ Fig. S1]: we initialize a particle with unit tangent velocity on a triangle mesh surface approximating a spherical surface of unit radius; we use a large 11 integration time step of 2, and after enough folding, the particle moves back to its original position with a negligible error.…”

Section: Algorithmmentioning

confidence: 99%

A simulation algorithm for Brownian dynamics on complex curved surfaces

Yang

2019

The Journal of Chemical Physics

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Brownian dynamics of colloidal particles on complex surfaces has found important applications in diverse physical, chemical and biological processes. However, current Brownian dynamics simulation algorithms mostly work for relatively simple surfaces that can be analytically parameterized. In this work, we develop an algorithm to enable Brownian dynamics simulation on extremely complex surfaces. We approximate complex surfaces with triangle mesh surfaces and employ a novel scheme to perform particle simulation on these triangle mesh surfaces. Our algorithm computes forces and velocities of particles in global coordinates but updates their positions in local coordinates, which benefits from the advantages of simulation schemes in both global and local coordinate alone. We benchmark the proposed algorithm with theory and then simulate Brownian dynamics of both single and multiple particles on torus and knot surfaces. The results show that our method captures well diffusion, transport, and crystallization of colloidal particles on complex surfaces with non-trivial topology. This study offers an efficient strategy for elucidating the impact of curvature, geometry, and topology on particle dynamics and microstructure formation in complex environments.

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Emergent patterns of collective cell migration under tubular confinement

Cited by 121 publications

References 66 publications

Cell‐Perceived Substrate Curvature Dynamically Coordinates the Direction, Speed, and Persistence of Stromal Cell Migration

Cell‐Perceived Substrate Curvature Dynamically Coordinates the Direction, Speed, and Persistence of Stromal Cell Migration

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

A simulation algorithm for Brownian dynamics on complex curved surfaces

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