A cell can bind to itself and form a self-adhesion that can be engineered and harnessed as a new way to adhere cells to engineered materials-a key challenge for biomaterials are demonstrated. Here, a 3D structure smaller is developed than a single cell, that a Self-Adhesion-Tunnel (SAT) is called, that causes cells to wrap around it and bind to themselves. This process is driven through the cadherin proteins that regulate cell-cell adhesion, and it is shown that many of the key elements of a normal cell-cell adhesion are found in self-adhesions.
View Article and Find Full Text PDFReceptor tyrosine kinases (RTKs) play key roles in coordinating cell movement at both single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggests that these responses may be amenable to engineering-based control for sculpting tissue shape and function. Here, we report that a light-controlled epidermal growth factor (EGF) receptor (OptoEGFR) can be deployed in epithelial cells for precise, programmable control of long-range tissue movements.
View Article and Find Full Text PDFDespite the widespread popularity of the "scratch assay," where a pipette is dragged manually through cultured tissue to create a gap to study cell migration and healing, it carries significant drawbacks. Its heavy reliance on manual technique can complicate quantification, reduce throughput, and limit the versatility and reproducibility. We present an open-source, low-cost, accessible, robotic scratching platform that addresses all of the core issues.
View Article and Find Full Text PDFThe ability to precisely pattern cells and proteins is crucial in various scientific disciplines, including cell biology, bioengineering, and materials chemistry. Current techniques, such as microcontact stamping, 3D bioprinting, and direct photopatterning, have limitations in terms of cost, versatility, and throughput. In this Article, we present an accessible approach that combines the throughput of photomask systems with the versatility of programmable light patterning using a low-cost consumer LCD resin printer.
View Article and Find Full Text PDFEpithelial tissues sheath organs and electro-mechanically regulate ion and water transport to regulate development, homeostasis, and hydrostatic organ pressure. Here, we demonstrate how external electrical stimulation allows us to control these processes in living tissues. Specifically, we electrically stimulate hollow, 3D kidneyoids and gut organoids and find that physiological-strength electrical stimulation of ∼ 5 - 10 V/cm powerfully inflates hollow tissues; a process we call electro-inflation.
View Article and Find Full Text PDFJ R Soc Interface
March 2024
Epithelial monolayers are some of the best-studied models for collective cell migration due to their abundance in multicellular systems and their tractability. Experimentally, the collective migration of epithelial monolayers can be robustly steered using electric fields, via a process termed electrotaxis. Theoretically, however, the question of how to design an electric field to achieve a desired spatiotemporal movement pattern is underexplored.
View Article and Find Full Text PDFCells attach to the world through either cell-extracellular matrix adhesion or cell-cell adhesion, and traditional biomaterials imitate the matrix for integrin-based adhesion. However, materials incorporating cadherin proteins that mimic cell-cell adhesion offer an alternative to program cell behavior and integrate into living tissues. We investigated how cadherin substrates affect collective cell migration and cell cycling in epithelia.
View Article and Find Full Text PDFCells attach to the world around them in two ways-cell:extracellular-matrix adhesion and cell:cell adhesion-and conventional biomaterials are made to resemble the matrix to encourage integrin-based cell adhesion. However, interest is growing for cell-mimetic interfaces that mimic cell-cell interactions using cadherin proteins, as this offers a new way to program cell behavior and design synthetic implants and objects that can integrate directly into living tissues. Here, we explore how these cadherin-based materials affect collective cell behaviors, focusing specifically on collective migration and cell cycle regulation in cm-scale epithelia.
View Article and Find Full Text PDFJ R Soc Interface
July 2023
Although tissues are usually studied in isolation, this situation rarely occurs in biology, as cells, tissues and organs coexist and interact across scales to determine both shape and function. Here, we take a quantitative approach combining data from recent experiments, mathematical modelling and Bayesian parameter inference, to describe the self-assembly of multiple epithelial sheets by growth and collision. We use two simple and well-studied continuum models, where cells move either randomly or following population pressure gradients.
View Article and Find Full Text PDFTissues do not exist in isolation-they interact with other tissues within and across organs. While cell-cell interactions have been intensely investigated, less is known about tissue-tissue interactions. Here, we studied collisions between monolayer tissues with different geometries, cell densities, and cell types.
View Article and Find Full Text PDFMechanical ventilators are safety-critical devices that help patients breathe, commonly found in hospital intensive care units (ICUs)-yet, the high costs and proprietary nature of commercial ventilators inhibit their use as an educational and research platform. We present a fully open ventilator device-The People's Ventilator: PVP1-with complete hardware and software documentation including detailed build instructions and a DIY cost of $1,700 USD. We validate PVP1 against both key performance criteria specified in the U.
View Article and Find Full Text PDFPLoS Comput Biol
April 2022
Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the 'rules' behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that is intuitive to the researcher. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors-epithelial, endothelial, and metastatic breast cancer cells-and show how the results complement traditional biophysical approaches.
View Article and Find Full Text PDFThe ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration 'command' differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate 'rightward' via electrotaxis.
View Article and Find Full Text PDFIntroduction: Mechanical forces regulate many facets of cell and tissue biology. Studying the effects of forces on cells requires real-time observations of single- and multi-cell dynamics in tissue models during controlled external mechanical input. Many of the existing devices used to conduct these studies are costly and complicated to fabricate, which reduces the availability of these devices to many laboratories.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2021
Tardigrades must negotiate heterogeneous, fluctuating environments and accordingly utilize locomotive strategies capable of dealing with variable terrain. We analyze the kinematics and interleg coordination of freely walking tardigrades (species: ). We find that tardigrade walking replicates several key features of walking in insects despite disparities in size, skeleton, and habitat.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2021
As collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, preexisting collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue-electrical stimulation and electrotaxis-to primary mouse skin monolayers where we can tune cell-cell adhesion strength to modulate endogenous collectivity.
View Article and Find Full Text PDFThere is a growing interest in bioelectric wound treatment and electrotaxis, the process by which cells detect an electric field and orient their migration along its direction, has emerged as a potential cornerstone of the endogenous wound healing response. Despite recognition of the importance of electrotaxis in wound healing, no experimental demonstration to date has shown that the actual closing of a wound can be accelerated solely by the electrotaxis response itself, and in vivo systems are too complex to resolve cell migration from other healing stages such as proliferation and inflammation. This uncertainty has led to a lack of standardization between stimulation methods, model systems, and electrode technology required for device development.
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