# Incidence of Phage Capsid Organization on the Resistance to High Energy Proton Beams  
[PERSON]  
1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; [EMAIL_ADDRESS] (V.Z. ); [EMAIL_ADDRESS] (C.G. ); [EMAIL_ADDRESS] (M.G.R. ); [EMAIL_ADDRESS] (S.P.G. ); [EMAIL_ADDRESS] (D.F.) [PERSON]  
4 Department of Mathematics and Physics \"[PERSON]\"--CEDAD (Centre of Applied Physics, DAting and Diagnostics), University of Salento, 73100 Lecte, Italy; [EMAIL_ADDRESS]  
4 Department of Neutron Physics, Institute of Nuclear Physics, v.v.i., Husine-Re2 130, 250 68 Rez, Czech Republic; [EMAIL_ADDRESS] (V.H. ); [EMAIL_ADDRESS] (A.M.)  
5 Department of Physics, Faculty of Science, J. E. Purkyne University, Pasteurova 3544/1, 400 96 Usti nad Labem, Czech Republic. that are often slowed down due to the difficulties related to cultivation techniques and/or high contagiousness. Bacteriophages (or shortly phages) represent models extremely useful for understanding the molecular mechanisms involved in the stability of viral capsids and the resistance to different stresses. Similar to mammalian virus, phage resistance to environmental stresses is closely related to the protein composition of the external structure, named capsid, which encloses and protects the viral nucleic acid. In addition, it is known that the dynamic rearrangements or disassembly of capsid can affect the nucleic acid release in the host, consequently determining the success or failure of the infectious process [6]. The most common capsid geometries are icosahedral or helical symmetry. In the first case, the nucleic acid of a virus is packaged completely within a geometric shape with 20 sides with morphological units (capsomeres) arising from the interaction of proteins within the repeated structural units [7]. Differently to this, the helical array winds around the nucleic acid, following a similar spiral path, and can require only one nucleocapsid protein. Since a single alteration in the capsid proteins' subunits affect the stability of the entire phage particle, the use of helical phages, engineered to express specific changes on known portions of their protein subunits, could help to identify the cause-effect relationships between specific mutations and new structural rearrangements in the capsid. M13 phage has been widely used in several applications due to its nontoxic, self-assembling and specific binding properties. The small DNA and use as a vector for constructing phage libraries displaying billions of random peptides on the phage surface, made this phage (together with the other filamentous phages fd and f1) a model system in molecular biology and a versatile tool in genetic engineering and biotechnology [8]. The capsid of M13 phage, characterized by a helical symmetry structure, is mainly constituted by the major coat protein pVIII, which is responsible for the integrity of the phage. Vector systems-based phage libraries 88 or 8 + 8 result in a hybrid structure with a mixture of recombinant and wild-type pVIII molecules on the phage capsid [9]. The use of these random phage libraries is being increased in many biotechnological applications, such as marker discovery in vitro or in vivo [10, 11], surface functionalization for biosensors [12, 13, 14], as specific scaffolds for tissue-regeneration [15], immunization [16], drug targeting [17, 18] and hybrid materials [19, 20, 21, 22]. However, since M13 capsid is approximately composed by 2700 copies of the major coat protein pVIII, the virion particles could show a remarkable degree of conformational instability and/or metastability when engineered on pVIII protein [23]. The capsid structure has been suggested to be responsible for the great resistance of M13 to various physical and chemical stresses [20, 24, 25].