Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

Aramesh, Morteza; Stoycheva, Diana; Sandu, Ioana; Ihle, Stephan J.; Zünd, Tamara; Shiu, Jau-Ye; Forró, Csaba; Asghari, Mohammad; Bernero, Margherita; Lickert, Sebastian; Oxenius, Annette; Vogel, Viola; Klotzsch, Enrico

doi:10.1101/2021.04.19.440349

Cited by 6 publications

(5 citation statements)

References 52 publications

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“…Moreover, TCRs were clearly localized through the microvilli stems and tips, which are enriched with ezrin and F-actin, and were released through long rod-shaped fragments. Furthermore, it is now generally accepted that microvilli play an important role in sensing, particularly at the interface with the APCs ( 12, 30, 35 ).…”

Section: Discussionmentioning

confidence: 99%

Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion

Park

Kim

Soh

et al. 2022

Preprint

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Internalization of the T-cell antigen receptor (TCR) is intimately linked to T-cell activation: a phenomenon thought to be related to the “exhaustion” of T-cell responses. To date, however, no report has considered that during physical interaction with cognate antigen-presenting cells, T cells release many TCRs via T-cell microvilli particles, which are derived from finger-like membrane structures (microvilli) in a combined process of trogocytosis and enzymatic vesiculation and correspond with the loss of membrane TCRs and many external membrane components. Surprisingly, in contrast to TCR internalization, this event leads to rapid upregulation of surface TCRs and remarkable metabolic reprogramming of cholesterol and fatty acids synthesis to meet the demands of clonal expansion, which drives multiple rounds of division and cell survival. We called this event “trogocytic-molting,” which represents an intrinsic molecular basis of T-cell clonal expansion by which T cells gain increased sensitivity to low antigen concentrations.TEASER“Trogocytic-molting,” led to the rapid upregulation of surface TCRs and tremendous metabolic reprogramming to meet the demands of clonal expansion.

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Section: Discussionmentioning

confidence: 99%

Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion

Park

Kim

Soh

et al. 2022

Preprint

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“…Regulations of T cell activation upon nanoconfinement of microvilli into nanoarchitected pores was demonstrated by Aramesh and co‐workers. [ 108 ] Through forming small actin‐rich protrusions (microvilli), T cells respond to local environments as seen in signaling and antigen recognition. This study revealed that microvilli was favorably formed at nanoporous surfaces, resulting in changes of gene expression of the T cells accompanied with T cell activation.…”

Section: Mechanical Control Of Biosystemsmentioning

confidence: 99%

Mechano‐Nanoarchitectonics: Design and Function

Ariga

2022

Small Methods

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Mechanical stimuli have rather ambiguous and less‐specific features among various physical stimuli, but most materials exhibit a certain level of responses upon mechanical inputs. Unexplored sciences remain in mechanical responding systems as one of the frontiers of materials science. Nanoarchitectonics approaches for mechanically responding materials are discussed as mechano‐nanoarchitectonics in this review article. Recent approaches on molecular and materials systems with mechanical response capabilities are first exemplified with two viewpoints: i) mechanical control of supramolecular assemblies and materials and ii) mechanical control and evaluation of atom/molecular level structures. In the following sections, special attentions on interfacial environments for mechano‐nanoarchitectonics are emphasized. The section entitled iii) Mechanical Control of Molecular System at Dynamic Interface describes coupling of macroscopic mechanical forces and molecular‐level phenomena. Delicate mechanical forces can be applied to functional molecules embedded at the air–water interface where operation of molecular machines and tuning of molecular receptors upon macroscopic mechanical actions are discussed. Finally, the important role of the interfacial media are further extended to the control of living cells as described in the section entitled iv) Mechanical Control of Biosystems. Pioneering approaches on cell fate regulations at liquid–liquid interfaces are discussed in addition to well‐known mechanobiology.

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“…[ 57,58 ] Our recent publication using nanoporous substrates, led to a strongly enhanced T cell activation and proliferation, compared to flat substrates. [ 59 ] Together the signal processes mediated through microvilli represent potential targets for immune therapies as well as to facilitate an enhanced tumor infiltration and killing capacity.…”

Section: Ecm Microarchitecture and Stiffness Influence T Cell Activat...mentioning

confidence: 99%

The solid tumor microenvironment—Breaking the barrier for T cells

Simsek

Klotzsch

2022

BioEssays

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The tumor microenvironment (TME) plays a pivotal role in the behavior and development of solid tumors as well as shaping the immune response against them. As the tumor cells proliferate, the space they occupy and their physical interactions with the surrounding tissue increases. The growing tumor tissue becomes a complex dynamic structure, containing connective tissue, vascular structures, and extracellular matrix (ECM) that facilitates stimulation, oxygenation, and nutrition, necessary for its fast growth. Mechanical cues such as stiffness, solid stress, interstitial fluid pressure (IFP), matrix density, and microarchitecture influence cellular functions and ultimately tumor progression and metastasis. In this fight, our body is equipped with T cells as its spearhead against tumors. However, the altered biochemical and mechanical environment of the tumor niche affects T cell efficacy and leads to their exhaustion. Understanding the mechanobiological properties of the TME and their effects on T cells is key for developing novel adoptive tumor immunotherapies.

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Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

Cited by 6 publications

References 52 publications

Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion

Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion

Mechano‐Nanoarchitectonics: Design and Function

The solid tumor microenvironment—Breaking the barrier for T cells

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