Nanoscale E-Cadherin Ligand Patterns Show Threshold Size for Cellular Adhesion and Adherence Junction Formation

Kristensen, Stine H.; Pedersen, Gitte A.; Nejsum, Lene N.; Sutherland, Duncan S.

doi:10.1021/nl300514v

Cited by 16 publications

(18 citation statements)

References 27 publications

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“…Colloidal bead lithography has been proposed as an alternative, and has been used either with gold chemistry 38 or with an all-organic approach 39 . The latter metal-free approach is compatible with TIRF and RICM imaging 39,40 , and is the technique of choice here.…”

Section: Introductionmentioning

confidence: 99%

Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization

Dillard

Lellouch

et al. 2016

Integr. Biol.

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We investigate the adhesion and molecular organization of the plasma membrane of T lymphocytes interacting with a surrogate antigen presenting cell comprising glass supported ordered arrays of antibody (α-CD3) nano-dots dispersed in a non-adhesive matrix of polyethylene glycol (PEG). The local membrane adhesion and topography, as well as the distribution of the T cell receptors (TCRs) and the kinase ZAP-70, are influenced by dot-geometry, whereas the cell spreading area is determined by the overall average density of the ligands rather than specific characteristics of the dots. TCR clusters are recruited preferentially to the nano-dots and the TCR cluster size distribution has a weak dot-size dependence. On the patterns, the clusters are larger, more numerous, and more enriched in TCRs, as compared to the homogeneously distributed ligands at comparable concentrations. These observations support the idea that non-ligated TCRs residing in the non-adhered parts of the proximal membrane are able to diffuse and enrich the existing clusters at the ligand dots. However, long distance transport is impaired and cluster centralization in the form of a central supramolecular cluster (cSMAC) is not observed. Time-lapse imaging of early cell-surface contacts indicates that the ZAP-70 microclusters are directly recruited to the site of the antibody dots and this process is concomitant with membrane adhesion. These results together point to a complex interplay of adhesion, molecular organization and activation in response to spatially modulated stimulation.

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Section: Introductionmentioning

confidence: 99%

Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization

Dillard

Lellouch

et al. 2016

Integr. Biol.

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“…Generally, intermolecular interactions also play an important role in the self‐organization of cellular aggregates . In addition to introducing additional molecules such as oligonucleotides for directing cells organization, membrane proteins on epithelial cell surfaces, such as E‐cadherin mainly contribute to the binding capability of cellular cohesiveness from cells to cellular aggregates . To further explore the organization behavior of cellular aggregates from a molecular level, we carefully observed the variation in E‐cadherin at the contact region of two cellular aggregates.…”

Section: Resultsmentioning

confidence: 99%

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Luo

Meng

et al. 2019

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Self‐organization is a fundamental and indispensable process in a living system. To understand cell behavior in vivo such as tumorigenesis, 3D cellular aggregates, instead of 2D cellular sheets, have been employed as a vivid in vitro model for self‐organization. However, most focus on the macroscale wetting and fusion of cellular aggregates. In this study, it is reported that self‐organization of cells from simple to complex aggregates can be induced by multiscale topography through confined templates at the macroscale and cell interactions at the nanoscale. On the one hand, macroscale templates are beneficial for the organization of individual cells into simple and complex cellular aggregates with various shapes. On the other hand, the realization of these macro‐organizations also depends on cell interactions at the nanoscale, as demonstrated by the intimate contact between nanoscale pseudopodia stretched by adjacent frontier cells, much like holding hands and by the variation in the intermolecular interactions based on E‐cadherin. Therefore, these findings may be very meaningful for clarifying the organizational mechanism of tumor development, tissue engineering and regenerative medicine.

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“…Lateral clustering provides a signaling hub through interactions with other proteins, such as catenins, as well as a mechanical link to the actin cytoskeleton [ 54 ]. Using colloidal lithography, a threshold of 173 nm diameter patterns was estimated to be necessary for epithelial cell attachment to E-cadherin [ 55 ]. In order to understand the relationship between receptor density and the adhesive forces of cadherins, one study used self-assembled monolayers of thiols, to which they bound extracellular fragments of E-cadherin, and measured cell binding using single-molecule force spectroscopy (SMFS) [ 56 ].…”

Section: Nanoscale Cell Surface Receptor Regulation For Bio-instructive Therapeutic Designmentioning

confidence: 99%

Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization

Maynard

Winter

Cunnane

et al. 2020

Regen. Eng. Transl. Med.

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Regenerative medicine is aimed at restoring normal tissue function and can benefit from the application of tissue engineering and nano-therapeutics. In order for regenerative therapies to be effective, the spatiotemporal integration of tissue-engineered scaffolds by the native tissue, and the binding/release of therapeutic payloads by nano-materials, must be tightly controlled at the nanoscale in order to direct cell fate. However, due to a lack of insight regarding cell–material interactions at the nanoscale and subsequent downstream signaling, the clinical translation of regenerative therapies is limited due to poor material integration, rapid clearance, and complications such as graft-versus-host disease. This review paper is intended to outline our current understanding of cell–material interactions with the aim of highlighting potential areas for knowledge advancement or application in the field of regenerative medicine. This is achieved by reviewing the nanoscale organization of key cell surface receptors, the current techniques used to control the presentation of cell-interactive molecules on material surfaces, and the most advanced techniques for characterizing the interactions that occur between cell surface receptors and materials intended for use in regenerative medicine. Lay Summary The combination of biology, chemistry, materials science, and imaging technology affords exciting opportunities to better diagnose and treat a wide range of diseases. Recent advances in imaging technologies have enabled better understanding of the specific interactions that occur between human cells and their immediate surroundings in both health and disease. This biological understanding can be used to design smart therapies and tissue replacements that better mimic native tissue. Here, we discuss the advances in molecular biology and technologies that can be employed to functionalize materials and characterize their interaction with biological entities to facilitate the design of more sophisticated medical therapies.

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Nanoscale E-Cadherin Ligand Patterns Show Threshold Size for Cellular Adhesion and Adherence Junction Formation

Cited by 16 publications

References 27 publications

Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization

Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization

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