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

• 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
• Journal Title: ISCIENCE
• Volume: Volume 23, Number 11
• Publisher: CELL PRESS | 2020-11-20, Pages 101751-101751
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.isci.2020.101751
• Subjects: Biology, Cell; Biology, Genetics
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; ENDOTHELIAL-CELLS; E-SELECTIN; ROLLING ADHESION; P-SELECTIN; CARCINOEMBRYONIC ANTIGEN; HEMODYNAMIC FLOW; VARIANT ISOFORMS; GENE-EXPRESSION; CANCER-CELLS; MONOCYTES

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.