Manipulating mammalian cell morphologies using chemical-mechanical polished integrated circuit chips

Abstract

Tungsten chemical-mechanical polished integrated circuits were used to study the alignment and immobilization of mammalian (Vero) cells. These devices consist of blanket silicon oxide thin films embedded with micro- and nano-meter scale tungsten metal line structures on the surface. The final surfaces are extremely flat and smooth across the entire substrate, with a roughness in the order of nanometers. Vero cells were deposited on the surface and allowed to adhere. Microscopy examinations revealed that cells have a strong preference to adhere to tungsten over silicon oxide surfaces with up to 99% of cells adhering to the tungsten portion of the surface. Cells self-aligned and elongated into long threads to maximize contact with isolated tungsten lines as thin as 180 nm. The orientation of the Vero cells showed sensitivity to the tungsten line geometric parameters, such as line width and spacing. Up to 93% of cells on 10 μm wide comb structures were aligned within ± 20° of the metal line axis. In contrast, only ~22% of cells incubated on 0.18 μm comb patterned tungsten lines were oriented within the same angular interval. This phenomenon is explained using a simple model describing cellular geometry as a function of pattern width and spacing, which showed that cells will rearrange their morphology to maximize their contact to the embedded tungsten. Finally, it was discovered that the materials could be reused after cleaning the surfaces, while maintaining cell alignment capability.

Pattern-Dependent Mammalian Cell (Vero) Morphology on Tantalum/Silicon Oxide 3D Nanocomposites

“…Results have shown that cellular responses often depend on the mechanical properties, pattern structures, and surface chemistry of the microenvironment surrounding the cells [1,3,4,5,7,8,10,11,12,13,14,15,16,17,18,19,20]; however, work done thus far has been conducted with structures composed of monolithic materials having uniform surface chemical composition. Studies of cell behavior on nanocomposite surfaces are limited [1,3,17,18,19,20].…”

Limitation in Controlling the Morphology of Mammalian Vero Cells Induced by Cell Division on Asymmetric Tungsten-Silicon Oxide Nanocomposite

“…The chemical-mechanical polished (CMP) tungsten-silicon oxide nanocomposite was prepared with the same fabrication techniques described in our previous work [10] and supplied by Versum Materials, LLC (Tempe, AZ, USA). The process to fabricate the parallel line patterned structures is schematically illustrated in Figure S2.…”

“…Nanocomposites have a wide range of applications in electronics [1], mechanical structures [2][3][4], sensors [5], and bioengineering [6,7]. The ability to manipulate the behavior of biological cells by means of engineered nano-biomaterials is possible and effective [8][9][10][11][12][13][14][15]. Jahed et al [14] demonstrated that the shape of 3T3 Swiss albino fibroblasts can be influenced by patterns of microscale silicon pillars.…”

“…In addition to the overall shape of the cell, vertical pillars can also alter cell nuclear geometry in prostatic cancer cells (PC3) [11]. Moussa et al [10,15] showed that both mammalian kidney epithelial (Vero) and human dermal fibroblast cells (GM5565) elongate and align on smooth-flat silicon oxide surfaces embedded with parallel tungsten (W) lines. In addition, similar cell alignment morphology was observed in adherent Japanese quail fibrosarcoma cell line cells (QT-35) on these devices as shown in Figure S1.…”

“…In earlier work, Moussa et al [10] developed a mathematical model that predicts the alignment of Vero cells on simple smooth surfaces consisting of alternating tungsten and silicon oxide parallel lines. The model is based on maximizing the total surface area of the cell that can contact a preferred surface (in that case, a preference for tungsten).…”