Chemically Programmed Cell Adhesion with Membrane-Anchored Oligonucleotides

Selden, Nicholas S.; Todhunter, Michael E.; Jee, Noel Y.; Liu, Jennifer S.; Broaders, Kyle E.; Gartner, Zev J.

doi:10.1021/ja2080949

Cited by 141 publications

(144 citation statements)

References 25 publications

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“…3C and SI Appendix). To assay for self-organization, we forced aggregation of control LEP with p120 knockdown MEP by either mechanical or chemical means (SI Appendix) (22)(23)(24). Consistent with the predictions of the model, we observed a transition among tissue architectures in nonadhesive agarose: Instead of an inverted tissue architecture, the now less-cohesive MEP moved to the periphery of the tissue, allowing the control LEP to maximize their interactions at the tissue core (Fig.…”

Section: Human Mammary Epithelial Cells Can Self-organize Into An Invsupporting

confidence: 60%

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Developing tissues contain motile populations of cells that can selforganize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its selforganization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo-and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.heterogeneity | cell sorting | differential adhesion | mammary | prostate S elf-organization is a process that contributes to pattern formation and repair at all scales of biological complexity. At the tissue scale, defining robust strategies of self-organization is critical for engineering functional tissues, as well as for understanding development and the breakdown of tissue structure during diseases such as cancer (1). During development, two or more populations of motile cells can self-organize into spatially ordered tissues by a process referred to as cell sorting (2-4). The outcome of cell sorting can be rationalized using physical models that invoke cell-type-specific differences in interfacial energies. Interfacial energies arise through the action of a contractile cell cortex coupled to adhesion molecules (e.g., cadherins) that link the cortices of neighboring cells and signal to modulate cortical tension at specific cellular interfaces (5). In general, the organization of a tissue after cell sorting corresponds to a configuration that maximizes the formation of the most energetically favorable (hereafter referred to as most cell-cell cohesive) † cellular interfaces (6). For example, with an intermediate level of heterotypic cell-cell cohesion the most self-cohesive cell type is typically found in the tissue core, with the le...

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Section: Human Mammary Epithelial Cells Can Self-organize Into An Invsupporting

confidence: 60%

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…(B) Cell surfaces (7) and (8) were engineered to present ketones or oxyamines via liposome fusion and delivery. The tailored cells (9) and (10) were then mixed and formed rapid assemblies (11) via the bio-orthogonal oxime (15) click ligation. (C) List of liposomes, cells, and tailored cells used in the study.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…(5) or oxyamines (6) are added to the microwells. The liposomes rapidly fuse to the cells and deliver the functional groups to rapidly produce engineered cell surfaces presenting ketone (9) or oxyamine (10). (Middle) The engineered cells are then transferred to a simple microfluidic device.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Spheroid and Tissue Assembly via Click Chemistry in Microfluidic Flow

et al. 2015

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Proper cell-cell contact and communication are essential for the correct development and survival of higher order organisms. In order to study complex cell interactions that occur in vivo, model systems that are able to recapitulate 3D cell-cell interactions in vitro are key to advancing new biotechnologies, therapeutics, and tissue engineering applications. Herein, we show a new strategy to rapidly and efficiently generate complex multiple cell line containing spheroids and tissues in microfluidic flow without the use of scaffolds, molecular biology, or metabolic biosynthesis. The method relies on the integration of microfluidics, liposome fusion, bio-orthogonal chemistry, and cell surface engineering to rapidly click coculture cell assemblies in flow. We demonstrate this strategy by assembling various combinations of cell types with an interfacial cell to cell click chemistry in microfluidic flow to generate a range of spheroid types and oriented tissue multilayers.

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“…An alternative approach uses DNA as a synthetic adhesion molecule to produce 3D tissues with programmable connectivity (Fig. 3D) (Chandra et al, 2006;Gartner and Bertozzi, 2009;Hsiao et al, 2009;Selden et al, 2012;Teramura et al, 2010;Weber et al, 2014). In a recent advance, DNA-labeled cells were assembled onto a complementarily labeled glass surface that functioned as a spatial template, and the resulting aggregates were subsequently embedded into a 3D matrix to create tissues at single-cell resolution with defined size, shape, composition and initial spatial organization (Todhunter et al, 2015).…”

Section: D Bioprinting Enables Increased Spatial Control and Complexitymentioning

confidence: 99%

Dissecting the stem cell niche with organoid models: an engineering-based approach

2017

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For many tissues, single resident stem cells grown in vitro under appropriate three-dimensional conditions can produce outgrowths known as organoids. These tissues recapitulate much of the cell composition and architecture of the in vivo organ from which they derive, including the formation of a stem cell niche. This has facilitated the systematic experimental manipulation and single-cell, highthroughput imaging of stem cells within their respective niches. Furthermore, emerging technologies now make it possible to engineer organoids from purified cellular and extracellular components to directly model and test stem cell-niche interactions. In this Review, we discuss how organoids have been used to identify and characterize stem cell-niche interactions and uncover new niche components, focusing on three adult-derived organoid systems. We also describe new approaches to reconstitute organoids from purified cellular components, and discuss how this technology can help to address fundamental questions about the adult stem cell niche.

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Chemically Programmed Cell Adhesion with Membrane-Anchored Oligonucleotides

Cited by 141 publications

References 25 publications

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Spheroid and Tissue Assembly via Click Chemistry in Microfluidic Flow

Dissecting the stem cell niche with organoid models: an engineering-based approach

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