In this work, the interactions between block copolymer micelles (BCMs) and plasma membranes were investigated by performing coarse-grained molecular dynamics (CGMD) simulations. Different binding strengths between the BCMs and the membranes were tested, and four interaction pathways were discovered: attachment, semiendocytosis, endocytosis, and fusion. Endocytosis was the most efficient way for the BCMs to be taken up, and fusion could lead to cytotoxicity. Unlike rigid particles, deformation of the BCMs strongly affected the interaction pathways. We examined the effects of changing the aggregation number of the BCMs (N), the chain length of the polymer (N), and the chain stiffness of the hydrophobic block (k), and we learned that smaller N and lower N could lead to weaker cellular uptake capacities, whereas larger N and higher N gave rise to higher cytotoxicities. Moreover, a weaker chain stiffness of the hydrophobic block could be more favorable for obtaining BCMs with higher internalization efficacies and lower cytotoxicities. The results of these simulations could aid in the design of BCMs with desirable cellular internalization capacities and lower cytotoxicities. Such BCMs could be useful in drug-delivery systems.

The cellular internalization of rod-like nanoparticles (NPs) is investigated in a combined experimental and simulation study. These rod-like nanoparticles with smooth, abacus-like (i.e., beads-on-wires), and helical surface patterns are prepared by the cooperative self-assembly of poly(γ-benzyl-l-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) block copolymers and PBLG homopolymers. All three types of NPs can be internalized via endocytosis. Helical NPs exhibit the best endocytic efficacy, followed by smooth NPs and abacus-like NPs. Coarse-grained molecular dynamics simulations are used to examine the endocytic efficiency of these NPs. The NPs with helical and abacus-like surfaces can be endocytosed via novel "standing up" (tip entry) and "gyroscope-like" (precession) pathways, respectively, which are distinct from the pathway of traditional NPs with smooth surfaces. This finding indicates that the cellular internalization capacity and pathways can be regulated by introducing stripe patterns (helical and abacus-like) onto the surface of rod-like NPs. The results of this study may lead to novel applications of biomaterials, such as advanced drug delivery systems.

Solvent-induced chain conformation of cyclic PFpC6P via the migration insertion polymerization of CpFe(CO)2(CH2)6PPh2 (FpC6P) in THF/hexane mixed solvents.

P(FpCP) (Fp: CpFe(CO); CP: propyl diphenyl phosphine) has a helical backbone, resulting from piano stool metal coordination geometry, which is rigid with intramolecular aromatic interaction of the phenyl groups. The macromolecule is hydrophobic, but the polarized CO groups can interact with water for aqueous self-assembly. The stiffness of P(FpCP), which is adjustable by temperature, is an important factor influencing the morphologies of kinetically trapped assemblies. P(FpCP) self-assembles in DMSO/water (10/90 by volume) into lamellae at 25 °C, vesicles at 40 °C and irregular aggregates at higher temperatures (60 and 70 °C). The colloidal stability decreases in the order of lamellae, vesicles and irregular aggregates. Dissipative particle dynamics (DPD) simulation reveals the same temperature-dependent self-assembled morphologies with an interior of hydrophobic aromatic groups covered with the metal coordination units. The rigid backbone at 25 °C accounts for the formation of the layered morphology, while the reduced rigidity of the same P(FpCP) at 40 °C curves up the lamellae into vesicles. At a higher temperature (60 or 70 °C), P(FpCP) behaves as a random coil without obvious amphiphilic segregation, resulting in irregular aggregates. The stiffness is, therefore, a crucial factor for the aqueous assembly of macromolecules without obvious amphiphilic segregation, which is reminiscent of the solution behavior observed for many hydrophobic biological macromolecules such as proteins.

We found that poly(γ-benzyl-L-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) rod-coil block copolymers and polystyrene (PS) homopolymers can cooperatively self-assemble into nano-spheres with striped patterns on their surfaces (strip-pattern-spheres) in aqueous solution. With assistance of dissipative particle dynamics simulation, it is discovered that the PS homopolymers form a spherical template core and the PBLG-b-PEG block copolymers assemble into striped patterns on the spherical surface. The hydrophobic PBLG rods are packed orderly in the strips, while the hydrophilic PEG blocks stabilize the strip-pattern-spheres in solution. Defects such as dislocations and disclinations can be observed in the striped patterns. Self-assembling temperature and sphere radius are found to affect defect densities in the striped patterns. A possible mechanism is proposed to illustrate how PBLG-b-PEG and PS cooperatively self-assemble into hierarchical spheres with striped patterns on surfaces.