Publications by authors named "Daniel J Cohen"

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.

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Receptor 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.

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Despite 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.

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The 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.

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Article Synopsis
  • The text discusses the traditional "scratch assay," a method used to study cell migration and healing by creating injury gaps in cultured tissue, highlighting the challenges of manual techniques that affect reproducibility and efficiency.
  • It introduces a new open-source, low-cost robotic scratching platform that overcomes these limitations, allowing for precise and reproducible scratches in various tissue types while maintaining high throughput.
  • The robotic system also offers innovative features like sculpting specific tissue shapes and facilitating complex co-culture experiments, enhancing its utility for advanced tissue engineering and cell research.
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  • Cell-cell interactions are more realistic in 3D environments compared to traditional 2D Petri dish setups.
  • The authors present a simple method for creating a 3D cell environment using a 2D extracellular matrix and a vertical boundary treated with E-cadherin.
  • This approach allows biology labs to study cell adhesion in a more natural, three-dimensional way without the need for complex equipment.
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  • Epithelial monolayers are important for studying how groups of cells move together, and they can be influenced by electric fields in a phenomenon called electrotaxis.
  • This research develops a mathematical model to predict how these cell layers respond to electric fields and uses optimal control theory to find the best electric field designs for various movement goals.
  • The study creates a comprehensive approach for controlling collective cell migration, which can help inform strategies for guiding cells with different external signals in the future.
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  • Understanding how cells grow and move is essential for development and tissue upkeep, but the link between cell growth regulation and their migration behavior is still unclear.
  • This research introduces a simple mathematical model that connects cell movement with their growth stages, considering how crowded tissue affects these processes.
  • The findings reveal that cells adjust their growth based on local density during specific phases of their cycle, and this relationship aligns with experimental data, offering valuable insights into cell behavior in different environments.
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Epithelial 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.

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Article Synopsis
  • Collective electrotaxis is when a group of cells, like an epithelial layer, moves in response to an electric field, and their migration speed varies in different areas.
  • The research presents a model to explain these varying speeds, focusing on competing cues within the tissue that affect migration rates.
  • The study also introduces a model that can predict how the size and shape of the tissue influence cell movement and suggests ways to design electric fields for specific patterns of migration in applications.
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  • Practical parameter identifiability is crucial for accurately predicting biological phenomena and understanding their mechanisms, especially when using mechanistic models.
  • This study applies a profile-likelihood approach to examine parameter identifiability in four variations of the Fisher-KPP model using data from cell invasion assays.
  • Findings reveal that more complex models are often harder to identify, sensitive to slight experimental changes, and require larger datasets, indicating that parameter identifiability should be prioritized alongside model fit and complexity in model selection.
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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.

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Cells 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.

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Cells 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.

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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.

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Tissues 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.

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Mechanical 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.

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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.

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The 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.

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Introduction: 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.

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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.

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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.

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There 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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