Implicit solvent coarse‐grained model of polyamidoamine dendrimers: Role of generation and pH

Abstract

Highly branched polymers such as polyamidoamine (PAMAM) dendrimers are promising macromolecules in the realm of nanobiotechnology due to their high surface coverage of tunable functional groups. Modeling efforts of PAMAM can provide structural and morphological properties, but the inclusion of solvents and the exponential growth of atoms with generations make atomistic simulations computationally expensive. We apply an implicit solvent coarse-grained model, called the Dry Martini force field, to PAMAM dendrimers. The reduced number of particles and the absence of a solvent allow the capture of longer spatiotemporal scales. This study characterizes PAMAM dendrimers of generations one through seven in acidic, neutral, and basic pH environments. Comparison with existing literature, both experimental and theoretical, is done using measurements of the radius of gyration, moment of inertia, radial distributions, and scaling exponents. Additionally, ion coordination distributions are studied to provide insight into the effects of interior and exterior protonation on counter ions. This model serves as a starting point for future designs of larger functionalized dendrimers.

The Martini Model in Materials Science

“…The models available range from simple linear polymers such as PEO (Figure 1D), [ 14,30,35–37 ] nylon‐6, [ 38 ] and PS, [ 28,29,39–41 ] over branched and hyperbranched polymers such as (grafted) polyamidoamine (PAMAM) [ 42–48 ] or polyethylenimine (PEI) dendrimers, [ 49–52 ] to conjugated polymers such as poly(3‐hexylthiophene) (P3HT, Figure 1F) [ 53 ] and block copolymers [ 32,54,55 ] such as PEO–PPO [ 32,56 ] or styrene– and diisobutylene–maleic acid copolymers. [ 57,58 ] Moreover, polymers have also been developed within the Dry Martini [ 59 ] version of the force field: examples include PEO, [ 60 ] PAMAM dendrimers, [ 61 ] and charged polysaccharide. [ 62 ] Within the Dry Martini model, water is represented implicitly rather than explicitly by CG particles.…”

“…[ 59 ] It has been shown to work well in the context of lipid bilayer simulations, [ 59 ] and it has also been successfully used for simulating polymers. [ 60–62 ] However, problems for example in polymer solvation have also been reported when using the Dry version of the model. [ 64 ] In general, re‐balancing of the interactions and introduction of friction comes at a price.…”

Dendronized vesicles: formation, self-organization of dendron-grafted amphiphiles and stability

“…The radius of gyration of the PAMAM dendrimers is found to increase in acidic environments. 11,19 Other studies use free energy calculations to measure the favorable interactions between PAMAM dendrimers and phospholipid bilayers. 20 In this study, the stability of vesicles encompassing PAMAM dendron-graed amphiphiles (PDAs) and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipids is examined.…”

Mechanisms underlying interactions between PAMAM dendron-grafted surfaces with DPPC membranes

“…47 The PAMAM dendron-graed surface was modeled at neutral pH. 36,48 The CG PAMAM dendron was composed of internal tertiary amine junctions, amide branches, terminal protonated primary amines (+1e) and a short hydrocarbon chain which connected the dendron to the supporting surface. 49 Hydrated chloride counter ions (À1e) were added to maintain the charge neutrality of the system.…”

“…The parameters were based upon those used in earlier studies. [34][35][36]41,48 A typical cell membrane can have large spatial variations in the bilayer tension. [50][51][52] To focus the investigation, we examine the interactions between a tensionless DPPC lipid bilayer with a PAMAM dendron-graed surface.…”