Development of a microengineered approach for quantitative assessment of intercelluar communication in cell doublets and microscale tissue models
Year: 2015
Type: article
Abstract: Intercellular communication plays important roles in maintaining structural and functional integrities of multicellular organisms.Among variant intercellular communication strategies, direct cell-to-cell communication via gap junction is performed by virtually all cell types in normal tissue.Understanding the mechanism of gap junction intercellular communication (GJIC) and its roles in various physiological and pathologic conditions is therefore the subject of extensive investigation.The predominant approaches for investigation of intercellular communications include examination of the expressions of gap junction proteins using molecular biological approaches, and assessment of gap junction permeability by measuring dye transfer, electrical conductance or metabolic cooperation.Although these approaches have proven successful in providing information of intercellular communication, they all suffer from some limitations that may restrict their applications in cardiac research, such as the inability to perform direct functional assessment, the insufficiency of spatial and temporal resolutions, or the incompatibility with high-throughput assays.Newly developed microengineering technologies, on the other hand, largely excel traditional methods in spatial and temporal resolutions.These technologies are capable of creating electromechanical components at the length scales comparable to live cells.Their advances may shed lights on functional assessments of intercellular performance iii and therefore provide powerful platforms for studying intercellular communication.The aim of this study is to develop a microengineered approach to enable quantitative assessment of intercellular communication in cell doublets and microscale tissue models.Cell doublets isolated from cardiac muscle with well-preserved intercellular junctions are used as a physiologically relevant model.Selective electrical stimulation and electromechanical measurement are integrated in an in vitro platform so that the contractile performance due to electrical stimulation and that due to intercellular mechanical transduction can be separated, thus enabling quantitative assessment of intercellular performance by providing direct measures of cell contractility.The microengineered platform is applied for quantitative assessment of intercellular communications of adult cardiac myocytes in aortocaval fistula (ACF)-induced volumeoverload heart failure model.The results reveal the therapeutic implications of this platform in optimizing treatment plans to improve contractile performance in various myocardium disorders.In addition, to perform quantitative assessment of intercellular communication in tissue constructs, microscale tissue models are developed by employing tissue engineering principles.The tissue scaffolds are fabricated by a novel method that combines the high-throughput manufacturing capability and the spatial patterning capability via technological combination of electrospray and microfabrication.The cells are then cultured on the tissue scaffolds to form microscale tissue models.Using the microengineered platform, the selective electrical stimulation is performed within these microscale tissue models for quantitatively assessing intercellular performance.
Author: Xu Zhang
Institution: The Ohio State University
Language: English
Topic: Connexins and lens biology
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2508002588