(328d) Morphogenesis and Flow-Induced Structure Evolution of Block Copolymer Vesicles: Entropic and Energetic Motifs

Renewed interest in block copolymer (BCP) self-assembly in solution was catalyzed in the 1990s by the pioneering discoveries of vesicular morphologies, referred to as polymersomes [1-5]. The nomenclature (polymersomes) is borrowed from the literature on biological vesicles, or liposomes, which are made up of amphiphilic phospholipid molecules. However, as summarized in the review by Bleul et al. [6], BCPs offer robust means of size control of the vesicles by varying the chemical composition and/or molecular weight of the copolymer chain, changing the polymer concentration, the addition of secondary molecules capable of inserting themselves into the assembly and act as spacers, as well as microfluidics-based flow manipulation to produce droplets of controllable sizes. Resultantly, polymersomes of sizes that range between several nanometers to tens of micrometers can be routinely manufactured with low degrees of polydispersity. Such morphologies form the building blocks of complex nanostructures that offer significant promise in nanomedicine for applications as drug carriers for targeted delivery of therapeutic agents to treat diseases including many cancers, in gene therapy, for breaching biological barriers such as the blood-brain barrier and intestinal epithelium, and as diagnostic agents [3, 6]. Many such applications involve flow-induced mechanical deformation of vesicular assemblies. To date, except for clues obtained from sparse experiments, mechanisms and morphological/rheological consequences of flow-microstructure interactions in solutions containing polymersomes remain poorly understood.

We use coarse-grained molecular dynamics (CGMD) simulations to study vesiculation in amphiphilic diblock BCP solutions. Subsequently, non-equilibrium CGMD simulations are employed to investigate morphological transitions in vesicular assemblies induced by steady and uniform shear flow. The simulations incorporate explicit solvent-mediated solvophilic/solvophobic interactions among the bcp molecules [7]. They are adapted from our previous work on structure and rheology of surfactant micelles in solution [8-15]. Vesiculation is facilitated through the following pathway: formation of spherical aggregates from a homogeneous copolymer solution, merger of spherical aggregates to form rod-like micelles, fusion of rods to form longer wormlike micelles, flattening of flexible cylindrical structures to form rectangular lamellae (bilayers) which further reorganize into disk-shaped lamellae, bending and curving of disk-like lamellae leading to cavity formation, and closure of the cavity to form vesicles. The simulation results qualitatively support the energetics motif proposed to explain vesicle formation from lamellar structures, i.e., the unfavorable solvophobic interactions along the edge of the lamella are eliminated at the expense of gaining curvature energy. However, significant quantitative differences exist between simulation predictions and estimates obtained based on ideal geometric representations for the change in hydrophobic surface area accompanying the rod-lamella-vesicle transition. Changes in information (Shannon) entropy, characterized by the expectation of the logarithm of the probability distribution functions (pdfs) of segmental stretch, are statistically insignificant along the transition pathway. These pdfs suggest a log-normal distribution of the segmental stretch parameter for rods, lamellae and polymersomes.

The effect of shear flow on morphology evolution of polymersomes is studied by systematically varying the Weissenberg number, Wi, defined as the ratio of the orientation relaxation time of the polymersomes to the inverse shear rate, and the flow strain. Shannon entropy associated with the segmental stretch and orientation is used to quantify flow-induced changes in entropy. Energetic variations are quantified by tracking the interfacial area between the solvophobic groups and solvent. Simulations reveal that above an O(1) critical Wi, flow-orientation and unfolding leads to the formation of a flattened structure which stretches along the direction of shear strain. For Wi = 3.6, the deformation for O(1) strain values leads to the formation of two rod-like micelles which are bridged by a shorter rod by an H-shaped junction [13]. For Wi = 7.3, deformation leads to a single elongated micelle structure with a non-homogeneous cross section. This is reminiscent of flow-induced transition from vesicles to thread-like micelles observed via cryo-TEM imaging in experiments [16]. In the presentation, we will discuss the mechanisms of unraveling and reorganization of the polymersome into flexible tubular (cylindrical) morphologies and network formation as well as accompanying rheological signatures. Further, we will also report on studies of structure recovery after flow cessation to explore the presence of hysteresis and persistent flow-induced structures [17-18].

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