Modulating T Cell Activation Using Depth Sensing Topographic Cues

Abstract

This report examines how sensing of substrate topography can be used to modulate T cell activation, a key coordinating step in the adaptive immune response. Inspired by the native T cell–antigen presenting cell interface, micrometer scale pits with varying depth are fabricated into planar substrates. Primary CD4+ T cells extend actin‐rich protrusions into the micropits. T cell activation, reflected in secretion of cytokines interleukin‐2 and interferon gamma, is sensitive to the micropit depth. Surprisingly, arrays of micropits with 4 μm depth enhance activation compared to flat substrates but deeper micropits are less effective at increasing cell response, revealing a biphasic dependence in activation as a function of feature dimensions. Inhibition of cell contractility abrogates the enhanced activation associated with the micropits. In conclusion, this report demonstrates that the 3D, microscale topography can be used to enhance T cell activation, an ability that most directly can be used to improve production of these cells for immunotherapy.

Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

“…While microstructured surfaces were shown to induce formation of membrane protrusions in T cells, [16][17][18] T cells reside in nanostructured environments, where they explore the nanoscale features of antigen presenting cells. To match with the membrane protrusions used by T cells, we studied the effect of nanotopographical constraints on microvilli formation in non-activated T cells.…”

Effect of Anisotropic Structural Depth on Orientation and Differentiation Behavior of Skeletal Muscle Cells

“…Myoblasts are typical anchoring-dependent cells, and their interaction with the microenvironment plays a crucial role in cellular behavior regulation and functional maintenance. Myoblasts are immersed in a complex microenvironment composed of various chemical and physical cues. − Among these cues, substrate topography has been proven to exert a profound influence on various cell behaviors, including orientation, migration, polarization, adhesion, and so on. − Many studies have been devoted to exploring the regulatory effects of topological patterns on cell behavior. ,− For example, micropillar arrays can change substrate stiffness and affect cell elongation and spreading, − while the shape and size of microwells can determine cell morphology . For muscle tissue regeneration, the uniform orientation of myoblasts plays a crucial role in ensuring the structural and functional integrity of muscle tissue. − Therefore, to achieve skeletal muscle regeneration in vitro, it is urgent to explore the influence of topological cues on the orientation regulation of myoblasts.…”

Poly(ε‐Caprolactone) Substrates with Micro/Nanohierarchical Patterned Structures for Cell Culture

“…Many studies have revealed the guiding role of interactions between cells and extracellular matrix (ECM) in regulating cellular behaviors. [8][9][10][11][12][13] As a dynamic and hierarchically organized composite, ECM is a complex physiological system composed of multilevel structures down to cellular (micrometer) and subcellular (nanoscale). [14] The critical component for studying cell-microenvironment interactions is to create, characterize, and manipulate dynamic microenvironmental cues in vitro down to a cellular and subcellular length scale.…”

“…[15] Recently, various biomaterial scaffolds have been created to study the interaction between cells and their surrounding microenvironment. [12][13][14][15][16][17][18] It was found that micro-or nanoscale features of substrates can affect cell adhesion, [19][20][21] differentiation, [22,23] proliferation, [24][25][26][27] migration, [28][29][30][31] morphology, [32,33] alignment, [34][35][36][37] and cytoskeleton organization. [38] Microscaled features influence cell growth through the alignment of cells with topographical features by the contact guide.…”