Selective adhesive cell capture without molecular specificity: new surfaces exploiting nanoscopic polycationic features as discrete adhesive units

Abstract

This work explored how molecularly non-specific polycationic nanoscale features on a collecting surface control kinetic and selectivity aspects of mammalian cell capture. Key principles for selective collector design were demonstrated by comparing the capture of two closely related breast cancer cell lines: MCF-7 and TMX2-28. TMX2-28 is a tamoxifen-selected clone of MCF-7. The collector was a silica surface, negatively-charged at pH 7.4, containing isolated molecules (~ 8 nm diameter) of the cationic polymer, poly(dimethyl-aminoethylmethacrylate), pDMAEMA. Important in this work is the non-selective nature of the pDMAEMA interactions with cells: pDMAEMA generally adheres negatively charged particles and cells in solution. We show here that selectivity towards cells results from collector design: this includes competition between repulsive interactions involving the negative silica and attractions to the immobilized pDMAEMA molecules, the random pDMAEMA arrangement on the surface, and the concentration of positive charge in the vicinity of the adsorbed pDMAEMA chains. The latter act as nanoscopic cationic surface patches, each weakly attracted to negatively-charged cells. Collecting surfaces engineered with an appropriate amount pDMAEMA, exposed to mixtures of MCF-7 and TMX2-28 cells preferentially captured TMX2-28 with a selectivity of 2.5. (This means that the ratio of TMX2-28 to MCF cells on the surface was 2.5 times their compositional ratio in free solution.) The ionic strength-dependence of cell capture was shown to be similar to that of silica microparticles on the same surfaces. This suggests that the mechanism of selective cell capture involves nanoscopic differences in the contact areas of the cells with the collector, allowing discrimination of closely related cell line-based small scale features of the cell surface. This work demonstrated that even without molecular specificity, selectivity for physical cell attributes produces adhesive discrimination.

Surfaces that Adhesively Discriminate Breast Epithelial Cell Lines and Lymphocytes in Buffer and Human Breast Milk

“…The culture medium and maintenance protocol for the breast cancer cell lines, MCF-7 and TMX2–28, were previously described. 28 MCF-10A was cultured in complete growth medium (MEGM cat # CC-3150 from Lonza/ Clonetics Corp. plus 10 ng/ mL cholera toxin). All 3 breast cell lines were grown as attached cultures in T-75 flasks, re-fed every 3 days and sub-cultured or prepared for experiments when 80 – 90% confluent using enzymatic treatment.…”

“…The MCF-10A, MCF-7, and Jurkat were obtained from ATCC, and the TMX2-28, a tamoxifen-resistant clone of MCF-7, was a gift from John Gierthy. The culture medium and maintenance protocol for the breast cancer cell lines, MCF-7 and TMX2-28, were previously described . MCF-10A was cultured in complete growth medium (MEGM cat # CC-3150 from Lonza/Clonetics Corp. plus 10 ng/mL cholera toxin).…”

“…The surfaces in the current work advance our prior surface designs targeting breast cell capture . We previously compared the capture of the closely related MCF-7 and TMX2-28 cell lines from buffer on surfaces that presented adhesive cationic charge clusters on a background surface that was anionic and substantially electrostatically repulsive.…”

Salivary Creatinine Detection Using a Cu(I)/Cu(II) Catalyst Layer of a Supercapacitive Hybrid Sensor: A Wireless IoT Device To Monitor Kidney Diseases for Remote Medical Mobility

“…Several types of polymer gels ,− with chemical and physical properties tailored over a wide range of characteristics are being employed in different sensory architectures, − such as flexible silk–fibroin sponges with distinctive pore structure and excellent water uptake, the hybrid of silk fibroin and carbon nanotube for cardiomyocyte functionalities, to achieve highly sensitive biomaterials. Therefore, considering the importance of salivary creatinine monitoring for CKD patients with severely chronic stages, we anticipated the benefit of using a novel matrix of supramolecular gels with metal nanoparticles as sensing material equipped with portable electrochemical-based smartphones that can be monitored closely by doctors, physicians, or any qualified practitioners.…”

Evidence of Cu(I) Coupling with Creatinine Using Cuprous Nanoparticles Encapsulated with Polyacrylic Acid Gel-Cu(II) in Facilitating the Determination of Advanced Kidney Dysfunctions

“…Polymer gels are well-known as soft matter and are employed as the next generation of smart and intelligent materials used in many new technological applications, such as biomedical devices, batteries (fuel cell), drug delivery, tissue engineering and bio/chemical sensors. − For instance, hydrogels with desired and chosen physical and chemical properties for specific biomedical applications can be used for selectively captured epithelial breast cancer cells or controlling surface-transport of staphylococcus . With the reinforcement of polymers and noble metals, researchers have obtained new materials that have exceptional and novel mechanical, electrical, and chemical behaviors .…”