4.7 Article

Tuning surface functionalization and collagen gel thickness to regulate cancer cell migration

期刊

COLLOIDS AND SURFACES B-BIOINTERFACES
卷 179, 期 -, 页码 37-47

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2019.03.031

关键词

Interface; Collagen; Adhesion; Morphology; MDA-MB-231; Migration; Durotaxis; Mechanotaxis; Haptotaxis

资金

  1. College of Engineering at Iowa State University
  2. Department of Materials Science and Engineering
  3. National Science Foundation Research Experience for Undergraduates [1560012]
  4. Div Of Engineering Education and Centers
  5. Directorate For Engineering [1560012] Funding Source: National Science Foundation

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Cancer cells have a tremendous ability to sense and respond to extracellular matrix (ECM) stiffness, modulating invasion. The magnitude of the sensed stiffness can either promote or inhibit the migration of cancer cells out of the primary tumor into surrounding tissue. Work has been done on examining the role of stiffness in tuning cancer cell migration by controlling elastic modulus in the bulk. However, a powerful and complementary approach for controlling stiffness is to leverage interactions between stiff-soft (e.g. glass-hydrogel) interfaces. Unfortunately, most work in this area probes cells in 2D environments. Of the reports that probe 3D environments, none have assessed the role of mechanical linkage to the interface as a potential handle in controlling local stiffness and cell behavior. In this paper, we examine the migration of cancer cells embedded in a collagen fiber network between two flat plates. We examine the role of both surface attachment of the collagen network to the stiff interface as well as thickness (50-540 mu m) of the collagen gel in driving collagen organization, cell morphology and cell migration. We find that surface attachment and thickness do not operate overlapping mechanisms, because they elicit different cell responses. While thickness and surface chemistry appear to control morphology, only thickness regulates collagen organization and cell migration speed. This suggests that surface attachment and thickness of the collagen gel control cell behavior through both collagen structure and local stiffness in confined fiber-forming networks.

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