Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions

Lippert, Anna; Dimov, Ivan B.; Winkel, Alexander; Humphrey, Jane; Chen, Kevin Y.; Santos, Ana Mafalda; Jenkins, Edward; Franze, Kristian; Davis, Simon J.; Klenerman, David

doi:10.1016/j.bpj.2020.11.021

Cited by 14 publications

(10 citation statements)

References 64 publications

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“…In this hypothetical setup, ICAM-1 is immobilized on a hexagonal gold nanoparticle array with defined interparticle spacing and pMHC is embedded onto a fluid bilayer ( 55 ). Further enhancing physiological relevance, the SLB could be deposited onto soft polydimethylsiloxane substrates mimicking the physiological relevant stiffnesses of APCs ( 56 ). These proposed experimental systems will enable a systemic investigation on how the immobilized pool of ICAM-1 alters the ability of naïve cells to discriminate antigens, T cell adhesion, TCR signaling, and actin dynamics.…”

Section: Discussionmentioning

confidence: 99%

The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

Pui‐Yan

Kellner

et al. 2022

Sci. Adv.

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T cells defend against cancer and viral infections by rapidly scanning the surface of target cells seeking specific peptide antigens. This key process in adaptive immunity is sparked upon T cell receptor (TCR) binding of antigens within cell-cell junctions stabilized by integrin (LFA-1)/intercellular adhesion molecule–1 (ICAM-1) complexes. A long-standing question in this area is whether the forces transmitted through the LFA-1/ICAM-1 complex tune T cell signaling. Here, we use spectrally encoded DNA tension probes to reveal the first maps of LFA-1 and TCR forces generated by the T cell cytoskeleton upon antigen recognition. DNA probes that control the magnitude of LFA-1 force show that F >12 pN potentiates antigen-dependent T cell activation by enhancing T cell–substrate engagement. LFA-1/ICAM-1 mechanical events with F >12 pN also enhance the discriminatory power of the TCR when presented with near cognate antigens. Overall, our results show that T cells integrate multiple channels of mechanical information through different ligand-receptor pairs to tune function.

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Section: Discussionmentioning

confidence: 99%

The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

Pui‐Yan

Kellner

et al. 2022

Sci. Adv.

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“…Although glass is the most commonly used substrate, poly(dimethylsiloxane) (PDMS) is also widely used owing to its unique features. PDMS can be easily customized via soft lithography, and thus it is a versatile platform for forming lipid bilayers with complex geometries. − Moreover, the controllable mechanical properties of PDMS can be tailored for studying various membrane features with PDMS-supported lipid bilayers. − In addition, PDMS-supported lipid bilayers are stable up to 132 h after preparation and hence are appropriate support for the above membrane applications.…”

Section: Introductionmentioning

confidence: 99%

A Study of the Effects of Plasma Surface Treatment on Lipid Bilayers Self-Spreading on a Polydimethylsiloxane Substrate under Different Treatment Times

et al. 2021

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Plasma-treated poly(dimethylsiloxane) (PDMS)-supported lipid bilayers are used as functional tools for studying cell membrane properties and as platforms for biotechnology applications. Self-spreading is a versatile method for forming lipid bilayers. However, few studies have focused on the effect of plasma treatment on self-spreading lipid bilayer formation. In this paper, we performed lipid bilayer self-spreading on a PDMS surface with different treatment times. Surface characterization of PDMS treated with different treatment times is evaluated by AFM and SEM, and the effects of plasma treatment of the PDMS surface on lipid bilayer self-spreading behavior is investigated by confocal microscopy. The front-edge velocity of lipid bilayers increases with the plasma treatment time. By theoretical analyses with the extended-DLVO modeling, we find that the most likely cause of the velocity change is the hydration repulsion energy between the PDMS surface and lipid bilayers. Moreover, the growth behavior of membrane lobes on the underlying self-spreading lipid bilayer was affected by topography changes in the PDMS surface resulting from plasma treatment. Our findings suggest that the growth of self-spreading lipid bilayers can be controlled by changing the plasma treatment time.

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“…Thus, mechanical stress from stiffness-based membrane deformation acts as a rheostat, leading to differential expression of genes involved in TCR/CD3 induced T cell functions 12 , 199 – 201 . However, pMHC and ICAM-1 on SLBs over soft (4 kPa) polydimethylsiloxane supports triggered early TCR signaling similarly to SLBs on stiff (GPa) glass supports 202 .…”

Section: Organization Of Membrane Proteins Involved In T Cell Activationmentioning

confidence: 92%

The interplay between membrane topology and mechanical forces in regulating T cell receptor activity

et al. 2022

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T cells are critically important for host defense against infections. T cell activation is specific because signal initiation requires T cell receptor (TCR) recognition of foreign antigen peptides presented by major histocompatibility complexes (pMHC) on antigen presenting cells (APCs). Recent advances reveal that the TCR acts as a mechanoreceptor, but it remains unclear how pMHC/TCR engagement generates mechanical forces that are converted to intracellular signals. Here we propose a TCR Bending Mechanosignal (TBM) model, in which local bending of the T cell membrane on the nanometer scale allows sustained contact of relatively small pMHC/TCR complexes interspersed among large surface receptors and adhesion molecules on the opposing surfaces of T cells and APCs. Localized T cell membrane bending is suggested to increase accessibility of TCR signaling domains to phosphorylation, facilitate selective recognition of agonists that form catch bonds, and reduce noise signals associated with slip bonds.

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Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions

Cited by 14 publications

References 64 publications

The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

A Study of the Effects of Plasma Surface Treatment on Lipid Bilayers Self-Spreading on a Polydimethylsiloxane Substrate under Different Treatment Times

The interplay between membrane topology and mechanical forces in regulating T cell receptor activity

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