Regulation of Cytoskeletal Dynamics during T Cell Activation by Substrate Stiffness

2018-03-07
Özçelikkale, Altuğ
Upadhyaya, Arpita
T lymphocytes are an integral part of the adaptive immune response. The detection of infectious agents critically depends on the interaction of T cells with antigen presenting cells, which have varying mechanical stiffness and complex topological features. It has been recently recognized that T cell activation is regulated both by stiffness of the antigen presenting surface and by cytoskeletal forces which partially arise from actomyosin contractility. However, the relationship between stiffness and the force generating machinery driving T cell activation is not well understood. To address this problem, we characterized actin and myosin dynamics during the activation of Jurkat T cells on stimulatory elastic substrates with variable stiffness using total internal reflection fluorescence (TIRF) and confocal microscopy. Activated T cells exhibit lamellipodial actin and myosin flows at the cell periphery as well as lamellar rings of actomyosin bundles. We have explored the stiffness-dependent organization of these distinct actomyosin structures and flows and their correlation with the spatiotemporal variation of traction stresses. This study provides insight into the potential role of stiffness in regulating cytoskeletal organization and force generation during T cell activation.
American Physical Society March Meeting

Suggestions

Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG
Yildiz, Soner; Alpdundar, Esin; Gungor, Bilgi; Kahraman, Tamer; Bayyurt, Banu; GÜRSEL, İHSAN; Gürsel, Mayda (2015-04-01)
Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA sensor STING (stimulator of IFN genes), initiating a response characterized by proinflammatory cytokine and type I IFN production. Strategies to improve the immune stimulatory activities of CDNs can further their potential for clinical development. Here, we demonstrat...
Effect of cortex stiffness variation on cleavage in animal cells
AKKAS, N; KERMANIAN, M (1993-09-29)
Cytokinesis is the division of the cytoplasm and the plasma membrane into two. Nuclear division and cytokinesis take a relatively short time to happen in animal cells in which cytokinesis takes place by means of furrowing. Here we consider the cleavage of the animal cells only. Although the basic division mechanisms appear to be similar in all animal cells, the divisions that take place during early embryonic development, which are termed as cleavages, are not exactly the same as those that occur later. In ...
REGULATION OF M2-TYPE PYRUVATE-KINASE FROM HUMAN MENINGIOMA BY ALLOSTERIC EFFECTORS FRUCTOSE 1,6 DIPHOSPHATE AND L-ALANINE
MELLATI, AA; YUCEL, M; ALTINORS, N; Gündüz, Ufuk (1992-01-01)
In the present study the mechanism of action of M2-type pyruvate kinase from human meningioma in the simultaneous presence of fructose 1,6 diphosphate and L-alanine was investigated. Purified pyruvate kinase from human meningioma was allosterically inhibited by L-alanine with respect to substrates phosphoenolpyruvate and ADP. The inhibitory effects of L-alanine was partially removed by fructose 1,6 diphosphate. The purified enzyme was slightly susceptible to ATP inhibition.
Effect of protein aggregation in the aqueous phase on the binding of membrane proteins to membranes
Doebler, R; Basaran, N; Goldston, H; Holloway, PW (Elsevier BV, 1999-02-01)
Analysis of the binding of hydrophobic peptides or proteins to membranes generally assumes that the solute is monomeric in both the aqueous phase and the membrane. Simulations were performed to examine the effect of solute self-association in the aqueous phase on the binding of monomeric solute to lipid vesicles. Aggregation lowered the initial concentration of monomeric solute, which was then maintained at a relatively constant value at the expense of the aggregated solute, as the lipid concentration was i...
Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides.
Klinman, DM; Zeuner, R; Yamada, H; Gürsel, Mayda; Currie, D; Gursel, I (Wiley, 2003-12-01)
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work exp...
Citation Formats
A. Özçelikkale and A. Upadhyaya, “Regulation of Cytoskeletal Dynamics during T Cell Activation by Substrate Stiffness,” presented at the American Physical Society March Meeting, California, Amerika Birleşik Devletleri, 2018, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/97062.