Effect of Macromolecular Crowding on the Conformation of Confined Chain Polymers Bruno Martı ´nez-Haya,* M. C. Gordillo Departamento de Ciencias Ambientales, Universidad Pablo de Olavide, 41013 Seville, Spain E-mail: bmarhay@upo.es, cgorbar@upo.es Received: April 23, 2005; Revised: June 23, 2005; Accepted: June 24, 2005; DOI: 10.1002/mats.200500025 Keywords: confinement; macromolecular crowding; nanopores; polymer conformation; polymer folding Introduction The conformation of a polymer largely determines its phy- sicochemical properties and behavior in condensed phases, and regulates function in the case of biological systems. Polymer conformation is influenced by internal as well as environmental factors, such as the structure and flexibility of the covalent backbone, or the competition between the interactions of the different sites of the polymer with each other, with neighboring particles and with the solvent. In addition, entropy (or free energy) constitutes one main driving force for polymer folding so that, especially under good solvent conditions, the combination of statistical fac- tors and excluded volume constraints efficiently control the conformation of the polymer. In this scenario, confine- ment [1] and macromolecular crowding [2] emerge as key factors for the control of conformational landscapes of polymers in natural or artificial environments, as well as for the enhancement or frustration of coil-globule, demixing or crystallization transitions. Interestingly, the effective forces exerted on a polymer by the confining medium can promote conformational changes that, depending on the pore geome- try, can be cooperative or opposite to the entropic excluded volume depletion effects. The rigorous theoretical treatment of mixtures of poly- mers and other molecules is, in general, complicated and computationally expensive. Usually, two limiting cases are considered, namely the colloid limit, where the macro- molecules present in the system have a greater size than the polymer, and the protein limit, where the crowding particles are smaller than the average size of the polymer. Whereas the colloid limit is relatively well characterized and specific approaches, such as the Asakura-Oosawa model [3] or the use of effective soft pair interaction potentials, [4] have been extensively explored, the behavior of colloid/polymer mix- tures in the protein limit, relevant to the present work, is less established. [5] The specific problem of polymer confine- ment has been the object of numerous investigations. In a seminal work, de Gennes performed extensive scaling analysis on the static properties of confined polymers. [1] Summary: The conformational behavior of flexible linear chain polymers confined in cylindrical pores and slab pores has been studied, employing a hard-bead chain model and a modification of a recently proposed recoil-growth bias Monte Carlo methodology, which improves the sampling efficiency in confined environments. It is found that the scaling law that correlates the unconstrained component of the radius of gyration of the polymer with the pore diameter in cylindrical pores is close but neatly different than the de Gennes mean- field value. The results also indicate that the addition of spherical particles with sizes within the protein limit may be employed to tune the folding of the confined polymer, since in this case the depletion constraints work against the effective stretching forces induced by confinement. Remarkably, the presence of the depleting particles at sufficiently high con- centration leads to appreciable changes in the exponents of the conformational scaling laws with respect to the uncrow- ded system. Conformational behavior of flexible hard-bead chain poly- mers confined in narrow pores. Macromol. Theory Simul. 2005, 14, 421–427 DOI: 10.1002/mats.200500025 ß 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Full Paper 421