Bioelectric stimulation controls tissue shape and size

Bioelectric stimulation controls tissue shape and size

05 April 2024 | Gawoon Shim, Isaac B. Breinyn, Alejandro Martinez-Calvo, Sameeksha Rao & Daniel J. Cohen
Electrically stimulating epithelial tissues can control their shape and size. This study demonstrates that applying external electrical fields to 3D kidneyoids and gut organoids leads to a process called electro-inflation, where tissues expand due to increased ion flux through channels and subsequent water flow into the lumen, generating hydrostatic pressure. The inflation is driven by field-induced ion crowding on the outer surface of the tissue, which increases ion transport and osmotic water flow. The study also shows that electrical stimulation breaks symmetry in 3D tissues, affecting their shape through electrotaxis, which is the directed migration of cells along electric field gradients. The ability of electrical cues to regulate tissue size and shape highlights the importance of the electrical micro-environment in living tissues. Epithelial tissues, which form the lining of organs, are electromechanical structures that regulate ion and water transport, maintaining homeostasis and hydrostatic pressure. The study used MDCK kidney cells to model epithelial structures and found that electrical stimulation caused rapid volumetric inflation, with the rate of inflation directly proportional to the electric field strength. The inflation was mediated by ion transport, leading to osmotic water flow and hydrostatic pressure. The study also showed that inhibiting ion channels/transporters reduced the inflation response, indicating that ion transport is crucial for the process. The study developed a computational model to explain the inflation process, showing that external electric fields can drive increased water transport. Confocal imaging revealed asymmetric deformation of cysts, which could be modulated by switching field polarity, attributed to 3D electrostatic migration towards the cathode. The electro-inflation response was generalized to other lumenized models, such as intestinal organoids, where CFTR-mediated ion transport was shown to be involved. The study also explored the mechanical aspects of electro-inflation, finding that the cysts behave like spherical pressure vessels, with hydrostatic pressure balanced by hoop stresses. Inhibiting actomyosin contractility increased the inflation rate and maximum volume. The study further showed that electrical stimulation induces electrotaxis, causing cells to migrate in response to electric fields, leading to asymmetry in tissue shape. This was confirmed by reversing electrotaxis with a PI3K inhibitor, showing that electrotaxis is the driver of asymmetry. The findings suggest that electrical stimulation can control tissue shape and size, highlighting the role of the electrical micro-environment in living tissues. The study has implications for developmental biology, biofabrication, and regenerative medicine, as it demonstrates the potential for external electrical control of epithelial tissues.Electrically stimulating epithelial tissues can control their shape and size. This study demonstrates that applying external electrical fields to 3D kidneyoids and gut organoids leads to a process called electro-inflation, where tissues expand due to increased ion flux through channels and subsequent water flow into the lumen, generating hydrostatic pressure. The inflation is driven by field-induced ion crowding on the outer surface of the tissue, which increases ion transport and osmotic water flow. The study also shows that electrical stimulation breaks symmetry in 3D tissues, affecting their shape through electrotaxis, which is the directed migration of cells along electric field gradients. The ability of electrical cues to regulate tissue size and shape highlights the importance of the electrical micro-environment in living tissues. Epithelial tissues, which form the lining of organs, are electromechanical structures that regulate ion and water transport, maintaining homeostasis and hydrostatic pressure. The study used MDCK kidney cells to model epithelial structures and found that electrical stimulation caused rapid volumetric inflation, with the rate of inflation directly proportional to the electric field strength. The inflation was mediated by ion transport, leading to osmotic water flow and hydrostatic pressure. The study also showed that inhibiting ion channels/transporters reduced the inflation response, indicating that ion transport is crucial for the process. The study developed a computational model to explain the inflation process, showing that external electric fields can drive increased water transport. Confocal imaging revealed asymmetric deformation of cysts, which could be modulated by switching field polarity, attributed to 3D electrostatic migration towards the cathode. The electro-inflation response was generalized to other lumenized models, such as intestinal organoids, where CFTR-mediated ion transport was shown to be involved. The study also explored the mechanical aspects of electro-inflation, finding that the cysts behave like spherical pressure vessels, with hydrostatic pressure balanced by hoop stresses. Inhibiting actomyosin contractility increased the inflation rate and maximum volume. The study further showed that electrical stimulation induces electrotaxis, causing cells to migrate in response to electric fields, leading to asymmetry in tissue shape. This was confirmed by reversing electrotaxis with a PI3K inhibitor, showing that electrotaxis is the driver of asymmetry. The findings suggest that electrical stimulation can control tissue shape and size, highlighting the role of the electrical micro-environment in living tissues. The study has implications for developmental biology, biofabrication, and regenerative medicine, as it demonstrates the potential for external electrical control of epithelial tissues.
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[slides and audio] Bioelectric stimulation controls tissue shape and size