Freezing or Wrapping: The Role of Particle Size in the Mechanism of Nanoparticle–Biomembrane Interaction

Understanding the interactions between nanoparticles (NPs) and biological matter is a high-priority research area because of the importance of elucidating the physical mechanisms underlying the interactions leading to NP potential toxicity as well as NP viability as therapeutic vectors in nanomedicine. Here, we use two model membrane systems, giant unilamellar vesicles (GUVs) and supported monolayers, to demonstrate the competition between adhesion and elastic energy at the nanobio interface, leading to different mechanisms of NP–membrane interaction relating to NP size. Small NPs (18 nm) cause a “freeze effect” of otherwise fluid phospholipids, significantly decreasing the phospholipid lateral mobility. The release of tension through stress-induced fracture mechanics results in a single microsize hole in the GUVs after interaction. Large particles (>78 nm) promote membrane wrapping, which leads to increased lipid lateral mobility and the eventual collapse of the vesicles. Electrochemical impedance spectroscopy on the supported monolayer model confirms that differently sized NPs interact differently with the phospholipids in close proximity to the electrode during the lipid desorption process. The time scale of these processes is in accordance with the proposed NP/GUV interaction mechanism

The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse-4

Tion of the two proteins in the TM neurons. In A, the ventral/lateral part of the TM nucleus is stained for HDC in red. In B the same area is stained for peripherin (green). The staining for the two proteins is digitally merged in C. Neurons that are stained for both HDC and peripherin appear yellow in this picture. Most neurons are stained for both antigens. Scale bar 20 μm.<p><b>Copyright information:</b></p><p>Taken from "The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse"</p><p>http://www.biomedcentral.com/1471-2202/9/26</p><p>BMC Neuroscience 2008;9():26-26.</p><p>Published online 24 Feb 2008</p><p>PMCID:PMC2266937.</p><p></p

The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse-0

In section hybridized with a S-labelled peripherin probe. The selective staining of the TM nucleus is evident. In B, a digoxigenin labelled mRNA probe reveals the distribution of peripherin expressing neurons in detail. The distribution is very similar to the histaminergic TM neurons. In C, neurons of the lateral TM that were hybridized simultaneously with a digoxigenin labelled probe for peripherin and a S-labelled probe for HDC are shown. The alkaline phosphatase staining for peripherin, which differentiate the neurons from the background, is colocalized with the silver grains that indicate the localization of HDC expression. 3 V, third ventricle. Scale bar 100 μm in B, 20 μm in C.<p><b>Copyright information:</b></p><p>Taken from "The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse"</p><p>http://www.biomedcentral.com/1471-2202/9/26</p><p>BMC Neuroscience 2008;9():26-26.</p><p>Published online 24 Feb 2008</p><p>PMCID:PMC2266937.</p><p></p

Artificial Nacre from Supramolecular Assembly of Graphene Oxide

Inspired by the “brick-and-mortar” structure and remarkable mechanical performance of nacre, many efforts have been devoted to fabricating nacre-mimicking materials. Herein, a class of graphene oxide (GO) based artificial nacre material with quadruple hydrogen-bonding interactions was fabricated by functionalization of polydopamine-capped graphene oxide (PDG) with 2-ureido-4­[1<i>H</i>]-pyrimidinone (UPy) self-complementary quadruple hydrogen-bonding units followed by supramolecular assembly process. The artificial nacre displays a strict “brick-and-mortar” structure, with PDG nanosheets as the brick and UPy units as the mortar. The resultant nanocomposite shows an excellent balance of strength and toughness. Because of the strong strengthening via quadruple hydrogen bonding, the tensile strength and toughness can reach 325.6 ± 17.8 MPa and 11.1 ± 1.3 MJ m^–3, respectively, thus exceeding natural nacre, and reaching 3.6 and 10 times that of a pure GO artificial nacre. Furthermore, after further H₂O treatment, the resulting H₂O-treated PDG-UPy actuator displays significant bending actuations when driven by heat. This work provides a pathway for the development of artificial nacre for their potential applications in energy conversion, temperature sensor, and thermo-driven actuator

Artificial Nacre from Supramolecular Assembly of Graphene Oxide

Inspired by the “brick-and-mortar” structure and remarkable mechanical performance of nacre, many efforts have been devoted to fabricating nacre-mimicking materials. Herein, a class of graphene oxide (GO) based artificial nacre material with quadruple hydrogen-bonding interactions was fabricated by functionalization of polydopamine-capped graphene oxide (PDG) with 2-ureido-4­[1<i>H</i>]-pyrimidinone (UPy) self-complementary quadruple hydrogen-bonding units followed by supramolecular assembly process. The artificial nacre displays a strict “brick-and-mortar” structure, with PDG nanosheets as the brick and UPy units as the mortar. The resultant nanocomposite shows an excellent balance of strength and toughness. Because of the strong strengthening via quadruple hydrogen bonding, the tensile strength and toughness can reach 325.6 ± 17.8 MPa and 11.1 ± 1.3 MJ m^–3, respectively, thus exceeding natural nacre, and reaching 3.6 and 10 times that of a pure GO artificial nacre. Furthermore, after further H₂O treatment, the resulting H₂O-treated PDG-UPy actuator displays significant bending actuations when driven by heat. This work provides a pathway for the development of artificial nacre for their potential applications in energy conversion, temperature sensor, and thermo-driven actuator

Effect of high protein diet challenge on MMA mice treated with vehicle or 5×10¹³ vg/kg mLB-001 at 8 weeks of age.

(A) Study design. Animals were maintained on the 12% protein diet and dosed with vehicle or mLB-001 at 8 weeks of age. At 3 months post-dosing, the diet was switched to the standard chow with 21% protein content and then to a 40% protein diet at 4 months post-dosing. Necropsy was performed at 6 months post-dosing when the mice were approximately 8 months old. (B) Kaplan-Meier survival curves of MMA mice show that the mLB-001-treated group survived longer than the vehicle-treated group (P = 0.052, Log-rank test). (C) Change in body weight of MMA mice in response to the high protein diet challenge. The body weight of each animal was normalized to its weight at the introduction of the 21% protein diet. Females and males were combined due to lack of significant difference. Animal numbers at each timepoint are indicated above the graph. * P 0.05, **** P 0.0001, mixed-effects analysis with multiple comparisons between vehicle- and mLB-001-treated groups at the indicated timepoints. (D) Circulating methylmalonic acid in the mLB-001-treated animals maintained at low levels but elevated in the vehicle-treated animals in response to high protein diet challenge. *** P 0.001, **** P 0.0001, mixed-effects analysis with multiple comparisons between vehicle- and mLB-001-treated groups at the indicated timepoints. (E) Plasma ALB-2A levels remained stable in the mLB-001-treated heterozygous animals while demonstrating exponential increases over time in the MMA mice.</p

MMUT holo-mutase activity in liver.

MMA mice (-/-) or heterozygous mice (+/-) were treated with 1×1014 vg/kg mLB-001 at PND 1 (D1) or 5×1013 vg/kg mLB-001 at 8 weeks of age (W8). Terminal samples were analyzed at 6 months post-dosing. The mutase activity unit is defined as the amount of the enzyme that converted methylmalonyl CoA to succinyl CoA (μmol/min), and the data were normalized by the total protein in the liver lysates. (TIF)</p

Body weight of MMA mice and their heterozygous littermates.

(A) Animals were dosed with vehicle or 1×1014 vg/kg mLB-001 on PND 1. Nursing dams were kept on the standard 21% protein diet until PND 14, when the diet was switched to a 12% protein diet. Pups were weaned on PND 28 and maintained on the 12% protein diet. At 3 months of age, all surviving animals were switched to the standard chow with 21% protein content and then to a 40% protein diet at 4 months of age. Animals were monitored until 6 months of age. (B) Animals were dosed with vehicle, 2.5×1013, 5×1013 or 1×1014 vg/kg mLB-001 on PND 1. Other procedures are the same as for (A). (C) Animals were maintained on the 12% protein diet and dosed with vehicle or 5×1013 vg/kg mLB-001 at 8 weeks of age. At 3 months post-dosing, the diet was switched to the standard chow with 21% protein content and then to a 40% protein diet at 4 months post-dosing. Animals were monitored until 8 months of age. (TIF)</p

Activities of MMA mice injected with vehicle or mLB-001.

Animals were injected with vehicle or 5×1013 vg/kg mLB-001 at 8 weeks of age. At 5 months post-dosing, two animals, one from each treatment group, were removed from their home cages and placed together in a freshly prepared cage. The video was recorded within 2 minutes of the animal placement in the cage. (GIF)</p

Analyses of terminal samples from animals treated with vehicle or mLB-001 at 6-month post-dosing.

MMA mice (-/-) or heterozygous mice (+/-) were treated with 1×1014 vg/kg mLB-001 at PND 1 (D1) or 5×1013 vg/kg mLB-001 at 8 weeks of age (W8). Terminal samples were analyzed at 6 months post-dosing. (A) Percentage of integrated albumin alleles in liver. (B) Fused mRNA expression in liver. (C) Circulating ALB-2A level. **** P 0.0001, Student’s t-test.</p