Introduction
The extracellular matrix (ECM) in the tumor microenvironment contains high densities of collagen that are highly aligned, resulting in directional migration called contact guidance that facilitates efficient migration out of the tumor. Cancer cells can remodel the ECM through traction force controlled by myosin contractility or proteolytic activity controlled by matrix metalloproteinase (MMP) activity, leading to either enhanced or diminished contact guidance.
Abstract Cancer cell metastasis is responsible for approximately 90% of deaths related to cancer. The migration of cancer cells away from the primary tumor and into healthy tissue is driven in part by contact guidance, or directed migration in response to aligned extracellular matrix. While contact guidance has been a focus of many studies, much of this research has explored environments that present 2D contact guidance structures. Contact guidance environments in 3D more closely resemble in viv...
Last. Ralf Kemkemer(Reutlingen University)H-Index: 25
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A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to pe...
Abstract Bulk tissue stiffness has been correlated with regulation of cellular processes and conversely cells have been shown to remodel their pericellular tissue according to a complex feedback mechanism critical to development, homeostasis, and disease. However, bulk rheological methods mask the dynamics within a heterogeneous fibrous extracellular matrix (ECM) in the region proximal to a cell (pericellular region). Here, we use optical tweezers active microrheology (AMR) to probe the distribu...
#1Ki Baek Lee(UCR: University of California, Riverside)H-Index: 4
#2Dong Hyun Nam(UCR: University of California, Riverside)H-Index: 11
Last. Xin Ge(UCR: University of California, Riverside)H-Index: 14
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Background As regulators of multifunctional metalloproteinases including MMP, ADAM and ADAMTS families, tissue inhibitors of metalloproteinases (TIMPs) play a pivotal role in extracellular matrix remodeling, which is involved in a wide variety of physiological processes. Since abnormal metalloproteinase activities are related to numerous diseases such as arthritis, cancer, atherosclerosis, and neurological disorders, TIMPs and their engineered mutants hold therapeutic potential and thus have bee...
Contact guidance on aligned substrates leads to directed cell migration through a poorly defined mechanism. Here the authors show that alignment of adhesion structures and F-actin generates anisotropic traction stress to drive directional migration, and cell-cell contact reduces force orientation and directional response.
#1De-Liang Yang(Nanjing University of Science and Technology)H-Index: 1
#2Fan-Xi Zeng(Nanjing University of Science and Technology)H-Index: 1
Last. Li Li(Nanjing University of Science and Technology)H-Index: 3
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Abstract Collagen fibrils and hydroxyapatite might recognize each other at the mesoscale by multiple cooperative interactions due to their intrinsically repetitive structured surfaces, and thus effectively directing the biomineralization, a biological process involving regulating the growth of bones, teeth and other organs. In this work, a simple technique was developed to prepare nanowire arrays of biological macromolecules by reversely using the biomineralization mechanism, with results simila...
Abstract Directed cell migration by contact guidance in aligned collagenous extracellular matrix (ECM) is a critical enabler of breast cancer dissemination. The mechanisms of this process are poorly understood, particularly in 3D, in part because of the lack of efficient methods to generate aligned collagen matrices. To address this technological gap, we propose a simple method to align collagen gels using guided cellular compaction. Our method yields highly aligned, acellular collagen construct...
Abstract During cancer progression the extracellular matrix is remodeled, forming aligned collagen fibers that proceed radially from the tumor, resulting in invasion. We have recently shown that different invasive breast cancer cells respond to epitaxially grown, aligned collagen fibrils differently. This article develops insight into why these cells differ in their contact guidance fidelity. Small changes in contractility or adhesion dramatically alter directional persistence on aligned collage...
: In vivo, geometric cues from the extracellular matrix (ECM) are critical for the regulation of cell shape, adhesion, and migration. During contact guidance, the fibrillar architecture of the ECM promotes an elongated cell shape and migration along the fibrils. The subcellular mechanisms by which cells sense ECM geometry and translate it into changes in shape and migration direction are not understood. Here we pattern linear fibronectin features to mimic fibrillar ECM and elucidate the mechanis...
Last. C. Sabarinath(PSG College of Technology)H-Index: 5
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The study of breast cancer metastasis is limited due to poor knowledge of molecular progression of breast tumor and varied heterogeneity. For a better understanding of tumor metastasis, a reliable 3D in vitro model bridging the gap between 2D cultures and in vivo animal model studies is essential. Our study is focused on two key points: (i) designing a 3D microenvironment for studying metastasis and (ii) simulating the metastasis milieu by inducing epithelial to mesenchymal transition (EMT) and ...
#1Yuqi Liang(Guangzhou University of Chinese Medicine)H-Index: 2
#2Zhihao Lv(Guangzhou University of Chinese Medicine)H-Index: 1
Last. Bin Wen(Guangzhou University of Chinese Medicine)H-Index: 5
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As the major component of the tumor matrix, collagen greatly influences tumor invasion and prognosis. The present study compared the remodeling of collagen and collagenase in 56 patients with colorectal cancer (CRC) using Sirius red stain and immunohistochemistry, exploring the relationship between collagen remodeling and the prognosis of CRC. Weak or strong changes in collagen fiber arrangement in birefringence were observed. With the exception of a higher density, weak changes equated to a sim...
Abstract Paper-based platforms for biological studies have received significant attention given that cellulose is ubiquitous, biocompatible, and can be readily organized into tunable fibrous structures. In the latter form, effect of complexity in surface morphologies (roughness, porosity and fiber organization) on cell-substrate interaction has not been thoroughly explored. We infer that altering the properties of a fibrous material should lead to significant changes in cellular microenvironment...
