SHAMS ET AL. VOL. 8 ’ NO. 1 ’ 188 –197 ’ 2014 www.acsnano.org 188 December 18, 2013 C 2013 American Chemical Society Actin Reorganization through Dynamic Interactions with Single-Wall Carbon Nanotubes Hengameh Shams, †,‡ Brian D. Holt, § Seyed Hanif Mahboobi, † Zeinab Jahed, † Mohammad F. Islam, ^ Kris Noel Dahl, §, ) and Mohammad R. K. Mofrad †,‡, * † Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California 94720, United States, ‡ Physical Biosciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, United States , § Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States, ^ Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States, and ) Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States T he design and engineering of nano- scale devices for biomedical applica- tions require a more thorough under- standing of principles governing physical phenomena at this scale. Due to their extra- ordinary mechanical, chemical, optical and thermal properties, carbon nanotube (CNT)- based devices have attracted major atten- tion in a variety of applications ranging from scaffolds for neural tissue growth to gene delivery. 1À5 More recently, studies have shown that CNT insertion in various cell types is possible, making them a promising tool for intracellular transport. 6À10 Due to their biocompatibility 11 and unique ability to translocate through the plasma mem- brane and the nuclear envelope, via the nuclear pore complex, 12 without harming cell viability, 6 CNTs have been used for the intracellular and nuclear delivery of various biological cargos such as proteins, peptides DNA, and nucleic acids. 7À10,13À17 CNTs can be synthesized as single- or multiple-layer tubular structures with a wide range of different properties. Single-wall carbon nanotubes (SWCNTs) are preferred for biomedical applications for reasons such as their high length to diameter aspect ratio, high axial stiffness, inactivity in chemical reactions and negligible fluctuations at body temperature. While several studies have examined the thermal, chemical and mechanical properties of CNTs, 18À21 for biological applications, where the introduc- tion of external agents can disrupt natural functionalities of cells and thus organs, the specificeffects of CNTs on the system beha- vior must be further explored. Moreover, in some cases the strength of CNT interaction might be of interest. For example, site spe- cific drug deliveries require modifications of CNTs by attaching other molecules and/or ions that increase binding affinities for tar- get molecules. 22 Such processes, usually referred to as functionalization, necessitate a detailed understanding of CNT interac- tions with both target and newly attached molecules. * Address correspondence to mofrad@berkeley.edu. Received for review June 6, 2013 and accepted December 18, 2013. Published online 10.1021/nn402865e ABSTRACT Single-wall carbon nanotubes (SWCNTs) have been widely used for biological applications in recent years, and thus, it is critical to understand how these inert nanomaterials influence cell behavior. Recently, it has been observed that cellular phenotypes such as proliferation, force generation and growth change upon SWCNT treatment, and SWCNTs directly affect the organization and redis- tribution of the actin cytoskeleton. However, the interactions between SWCNTs and actin at the molecular level or how this interaction changes actin structure remain largely unknown. Here, we investigated direct interaction of actin with SWCNT using all-atom molecular dynamics simulations and NIR spectroscopy of actin-dispersed SWCNTs. Actin can stably bind to the SWCNT surfaces via hydrophobic interactions but still allows nanotubes to slide and rotate on the actin surface. Our results establish several nanoscale conformational changes for the actinÀSWCNT complexes, and we suggest these changes likely induce reorganization of actin filaments observed at larger scales. KEYWORDS: actin . single-walled carbon nanotubes . molecular dynamics . cytoskeleton . near-infrared fluorescence spectroscopy ARTICLE