RESUMO
We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to protect the epithelium from viruses. When these polymers are applied to the epithelium, they localize on the apical surface due to the tight junction barriers, resulting in surface-only coating. Therefore, these polymers can prevent the entry of viruses into cells of the epithelium with minimal disturbance to lateral cell-cell interactions and organizations.
Assuntos
COVID-19 , Polímeros , Humanos , Polímeros/farmacologia , Antivirais/farmacologia , SARS-CoV-2 , Membrana CelularRESUMO
Chemical control of cell-cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified poly(ethylene glycol) (PEG-CLS), to cell membranes. We found that the repulsive forces introduced by these tethered polymers induced cell detachment from a substrate and allowed cell dispersion in a suspension, modulated the speed of cell migration, and improved the separation of cells from tissues. Our analyses showed that coating the cells with tethered polymers most likely generated two distinct repulsive forces, lateral tension and steric repulsion, on the surface, which were tuned by altering the polymer size and density. We modeled how these two forces are generated in kinetically distinctive manners to explain the various responses of cells to the coating. Collectively, our observations demonstrate mechanochemical regulation of cell adhesion and dispersion by simply adding polymers to cells without genetic manipulation or chemical synthesis in the cells, which may contribute to the optimization of chemical coating strategies to regulate various types of cell-cell interacting systems.
Assuntos
Polietilenoglicóis , Polímeros , Adesão Celular , Comunicação Celular , Membrana CelularRESUMO
BACKGROUND: The role of abscisic acid (ABA) as a possible activator of cold acclimation process was postulated since endogenous levels of ABA increase temporarily or constitutively during cold-hardening. Exogenous application of ABA has been known to induce freezing tolerance at ambient temperatures in in vitro systems derived from cold hardy plants. Yet, some cell cultures acquired much greater freezing tolerance by ABA than by cold whilst maintaining active growth. This raises questions about the relationships among ABA, cold acclimation and growth cessation. To address this question, we attempted to 1) determine whether exogenous ABA can confer freezing tolerance in chilling-sensitive rice suspension cells and seedlings, which obviously lack the mechanisms to acquire freezing tolerance in response to cold; 2) characterize this phenomenon by optimizing the conditions and compare with the case of cold hardy bromegrass cells. RESULTS: Non-embryogenic suspension cells of rice suffered serious chilling injury when exposed to 4°C. When incubated with ABA at the optimal conditions (0.5-1 g cell inoculum, 75 µM ABA, 25-30°C, 7-10 days), they survived slow freezing (2°C/h) to -9.0 ~ -9.3°C (LT50: 50% killing temperature) while control cells were mostly injured at -3°C (LT50: -0.5 ~ -1.5°C). Ice-inoculation of the cell suspension at -3°C and survival determination by regrowth confirmed that ABA-treated rice cells survived extracellular freezing at -9°C. ABA-induced freezing tolerance did not require any exposure to cold and was best achieved at 25-30°C where the rice cells maintained high growth even in the presence of ABA. ABA treatment also increased tolerance to heat (43°C) as determined by regrowth. ABA-treated cells tended to have more augmented cytoplasm and/or reduced vacuole sizes compared to control cultures with a concomitant increase in osmolarity and a decrease in water content. ABA-treated (2-7 days) in vitro grown seedlings and their leaves survived slow freezing to -3°C with only marginal injury (LT50: -4°C) whereas untreated seedlings were killed at -3°C (LT50: -2°C). CONCLUSIONS: The results indicate that exogenous ABA can induce some levels of freezing tolerance in chilling-sensitive rice cells and seedlings, probably by eliciting mechanisms different from low temperature-induced cold acclimation.