A 3D Microfabricated Scaffold System for Unidirectional Cell Migration

Abstract

The present study demonstrates unidirectional cell migration using a novel 3D microfabricated scaffold, as revealed by the uneven sorting of cells into an area of 1 mm × 1 mm. To induce unidirectional cell migration, it is important to determine the optimal arrangement of 3D edges, and thus, the anisotropic periodic structures of micropatterns are adjusted appropriately. The cells put forth protrusions directionally along the sharp edges of these micropatterns, and migrated in the protruding direction. There are three advantages to this novel system. First, the range of applications is wide, because this system effectively induces unidirectional migration as long as 3D shapes of the scaffolds are maintained. Second, this system can contribute to the field of cell biology as a novel taxis assay. Third, this system is highly applicable to the development of medical devices. In the present report, unique 3D microfabricated scaffolds that provoked unidirectional migration of NIH3T3 cells are described. The 3D scaffolds could provoke cells to accumulate in a single target location, or could provoke a dissipated cell distribution. Because the shapes are very simple, they could be applied to the surfaces of various medical devices. Their utilization as a cell separation technology is also anticipated.

Shape of scaffold controlling the direction of cell migration

“…4). Based on this, it was possible to ascertain how cells are unevenly distributed to the right, confirming cell migration in a single direction [36].…”

“…The association between micropattern shape and cell migration in a single direction, resulting in uneven cell distribution, was evaluated using time-lapse videos, which showed that 94% of cells were in the groove, and that migration toward the right (i.e., the direction from the apex angle to the base of an isosceles triangle) was high [36]. Cells in these grooves acquired characteristic adhesion morphologies that were not present on flat surfaces (Fig.…”

“…Following completion of this micropattern (Fig. 2D) [36], the cells in the groove were no longer trapped and began to migrate to the right. Maintenance of this basic shape resulted in cell migration in a single direction, even if cell size or spacing was slightly different.…”

Biointerfaces with ultrathin patterns for directional control of cell migration

“…However, these methods have limitations in terms of coverage, as they could only span over a short distance due to the finite dynamic range of cellular sensing. To overcome this limitation, a microfabricated scaffold with a triangular shape pattern was developed to induce unidirectional cell migration [ 49 ]. This resulted in 77% of embryonic mouse fibroblast NIH3T3 cells aligned with the micropattern and migrated in one direction.…”

Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis

“…ECM alignment dictates the polarization of focal adhesions and protrusions by localizing Rac activity, which controls tumor invasiveness and modulates collective ECM remodeling through its distinct pushing/pulling deformation within diverse tumor geometry ( Wang et al, 2018 ; Kim et al, 2020 ). Cells require multiple adaptation mechanism to navigate through a more complex and restrictive in 3D microenvironment compared to 2D migration ( Figure 2B ) ( Sunami et al, 2020 ). 3D cell migration involves interactions with neighboring cells, as demonstrated via photothermal ablation of the 3D wound healing model, inhomogeneities of the 3D ECM matrix (e.g., composition and structural features), and various signaling pathways that make it a more complex process than in 2D environments ( Figure 2C ) ( Devreotes and Horwitz, 2015 ; Xiao et al, 2019 ; Hayn et al, 2020 ; Palmiero et al, 2023 ).…”