Lymph Node Subcapsular Sinus Microenvironment-On-A-Chip Modeling Shear Flow Relevant to Lymphatic Metastasis and Immune Cell Homing

• Type of Material: Article
• Authors: Katherine G. Birmingham, Georgia Institute of Technology; Meghan J. O'Melia, Georgia Institute of Technology; Samantha Bordy, Georgia Institute of Technology; David Reyes Aguilar, Georgia Institute of Technology; Bassel El-Rayes, Emory University; Gregory Lesinski, Emory University; Susan N. Thomas, Georgia Institute of Technology
• Language: English
• Date: 2020-11-20
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.isci.2020.101751
• Title of Journal or Parent Work: ISCIENCE
• Volume: 23
• Issue: 11
• Start Page: 101751
• End Page: 101751
• Grant/Funding Information: This work was supported by National Institutes of Health (NIH) grants R01CA207619, R21CA202849, P30CA16058, and T32GM008433, a President's Undergraduate Research Award from Georgia Tech, and the National Science Foundation Research Experience for Undergraduate through Georgia Tech's Summer Undergraduate Research Education program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: CANCER-CELLS; Science & Technology; E-SELECTIN; GENE-EXPRESSION; Multidisciplinary Sciences; ROLLING ADHESION; ENDOTHELIAL-CELLS; Science & Technology - Other Topics; HEMODYNAMIC FLOW; VARIANT ISOFORMS; CARCINOEMBRYONIC ANTIGEN; MONOCYTES; P-SELECTIN
• Research Categories: Biology, Cell; Biology, Genetics

Abstract

A lymph node sinus-on-a-chip adhesion microfluidic platform that recapitulates the hydrodynamic microenvironment of the lymph node subcapsular sinus was engineered. This device was used to interrogate the effects of lymph node remodeling on cellular adhesion in fluid flow relevant to lymphatic metastasis. Wall shear stress levels analytically estimated and modeled after quiescent and diseased/inflamed lymph nodes were experimentally recapitulated using a flow-based microfluidic perfusion system to assess the effects of physiological flow fields on human metastatic cancer cell adhesion. Results suggest that both altered fluid flow profiles and presentation of adhesive ligands, which are predicted to manifest within the lymph node subcapsular sinus as a result of inflammation-induced remodeling, and the presence of lymph-borne monocytic cells may synergistically contribute to the dynamic extent of cell adhesion in flow relevant to lymph node invasion by cancer and monocytic immune cells during lymphatic metastasis.