{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:35:30Z","timestamp":1783629330366,"version":"3.55.0"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"95","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Robot."],"published-print":{"date-parts":[[2024,10,23]]},"abstract":"<jats:p>\n            Arrhythmogenic cardiomyopathy (ACM) is a leading cause of sudden cardiac death among young adults. Aberrant gap junction remodeling has been linked to disease-causative mutations in plakophilin-2 (\n            <jats:italic>PKP2<\/jats:italic>\n            ). Although gap junctions are a key therapeutic target, measurement of gap junction function in preclinical disease models is technically challenging. To quantify gap junction function with high precision and high consistency, we developed a robotic cell manipulation system with visual feedback from digital holographic microscopy for three-dimensional and label-free imaging of human induced pluripotent stem cell\u2013derived cardiomyocytes (iPSC-CMs). The robotic system can accurately determine the dynamic height changes in the cells\u2019 contraction and resting phases, microinject drug-treated healthy and diseased iPSC-CMs in their resting phase with constant injection depth across all cells, and deposit a membrane-impermeable dye that solely diffuses between cells through gap junctions for measuring the gap junction diffusion function. The robotic system was applied toward a targeted drug screen to identify gap junction modulators and potential therapeutics for ACM. Five compounds were found to dose-dependently enhance gap junction permeability in cardiomyocytes with\n            <jats:italic>PKP2<\/jats:italic>\n            knockdown. In addition, PCO 400 (pinacidil) reduced beating irregularity in a mouse model of ACM expressing mutant PKP2 (R735X). These results highlight the utility of the robotic cell manipulation system to efficiently assess gap junction function in a relevant preclinical disease model, thus providing a technique to advance drug discovery for ACM and other gap junction\u2013mediated diseases.\n          <\/jats:p>","DOI":"10.1126\/scirobotics.adm8233","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T17:58:26Z","timestamp":1729706306000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Robotic manipulation of cardiomyocytes to identify gap junction modifiers for arrhythmogenic cardiomyopathy"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9686-8597","authenticated-orcid":true,"given":"Wenkun","family":"Dou","sequence":"first","affiliation":[{"name":"Institute of Robotics and Intelligent Systems, Dalian University of Technology, Dalian, Liaoning, 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