Spatially and temporally controlled immune cell interactions using microscale tools

Dura, Burak; Voldman, Joel

doi:10.1016/j.coi.2015.05.006

Cited by 12 publications

(13 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…85–87 Moreover, microfluidic co-culture systems, including those based on valved microfluidics, 88 microfluidic cell trap arrays, 89 and droplet microfluidics, 90–91 have the ability to control cell-cell interactions at a single-cell resolution in a high-throughput manner by generating and manipulating cell pairs with hydrodynamic forces and/or other physical forces. 92–93 Such high-throughput, single-cell-level co-culture systems can simplify the complexity of cell-cell interactions and provide a wealth of information related to cell heterogeneity.…”

Section: The Cell Microenvironmentmentioning

confidence: 99%

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

et al. 2017

View full text Add to dashboard Cite

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

show abstract

Section: The Cell Microenvironmentmentioning

confidence: 99%

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Nanolitre micro-well arrays enable the study of single-cell phenotyping of rare cells, such as antigen-specific T cells and B cells. Studies on these rare subsets have revealed structure-function relationships between molecular synapses and signalling cascades [ 70 ]. Co-culture studies together with barcoded antibody arrays enabled the examination of the influence of paracrine signalling molecules on tumour cell function and signalling networks via the multiplexed detection of both intracellular and secreted proteins/cytokines [ 71 , 72 ].…”

Section: Enhanced Flow Cytometry Techniques For Single-cell Analysmentioning

confidence: 99%

Detecting Antigen-Specific T Cell Responses: From Bulk Populations to Single Cells

Phetsouphanh

Zaunders

Kelleher

2015

IJMS

View full text Add to dashboard Cite

A new generation of sensitive T cell-based assays facilitates the direct quantitation and characterization of antigen-specific T cell responses. Single-cell analyses have focused on measuring the quality and breadth of a response. Accumulating data from these studies demonstrate that there is considerable, previously-unrecognized, heterogeneity. Standard assays, such as the ICS, are often insufficient for characterization of rare subsets of cells. Enhanced flow cytometry with imaging capabilities enables the determination of cell morphology, as well as the spatial localization of the protein molecules within a single cell. Advances in both microfluidics and digital PCR have improved the efficiency of single-cell sorting and allowed multiplexed gene detection at the single-cell level. Delving further into the transcriptome of single-cells using RNA-seq is likely to reveal the fine-specificity of cellular events such as alternative splicing (i.e., splice variants) and allele-specific expression, and will also define the roles of new genes. Finally, detailed analysis of clonally related antigen-specific T cells using single-cell TCR RNA-seq will provide information on pathways of differentiation of memory T cells. With these state of the art technologies the transcriptomics and genomics of Ag-specific T cells can be more definitively elucidated.

show abstract

“…Cell-cell interactions are ubiquitous in organisms and can potentiate disease, but methods to selectively visualize and ultimately control them are lacking. [1][2][3] Current strategies rely on imaging with fluorescent proteins [4][5][6][7][8] or enzymatic labeling. [9][10][11][12] While useful, many of these methods are not generalizable to multiple cell types or provide only short-lived signals.…”

Section: Introductionmentioning

confidence: 99%

Caged Cumate Enables Proximity‐Dependent Control Over Gene Expression

2021

View full text Add to dashboard Cite

Cell-cell interactions underlie diverse physiological processes yet remain challenging to examine with conventional imaging tools. Here we report a novel strategy to illuminate cell proximity using transcriptional activators. We repurposed cumate, a small molecule inducer of gene expression, by caging its key carboxylate group with a nitrile. Nitrilase-expressing activator cells released the cage, liberating cumate for consumption by reporter cells. Reporter cells comprising a cumateresponsive switch expressed a target gene when in close proximity to the activator cells. Overall, this strategy provides a versatile platform to image and potentially manipulate cellular interactions over time.

show abstract

Spatially and temporally controlled immune cell interactions using microscale tools

Cited by 12 publications

References 56 publications

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Detecting Antigen-Specific T Cell Responses: From Bulk Populations to Single Cells

Caged Cumate Enables Proximity‐Dependent Control Over Gene Expression

Contact Info

Product

Resources

About