Introduction_NN1 Most_DAT cells_NN2 are_VBR adherent_NN1 and_CC must_VM attach_VVI to_II and_CC spread_VVN on_II a_AT1 surface_NN1 in_BCL21 order_BCL22 to_TO survive_VVI ,_, proliferate_JJ and_CC function_NN1 ._. 
In_II tissue_NN1 ,_, this_DD1 surface_NN1 is_VBZ the_AT extracellular_JJ matrix_NN1 (_( ECM_NP1 )_) ,_, an_AT1 insoluble_JJ scaffold_NN1 formed_VVN by_II the_AT assembly_NN1 of_IO several_DA2 large_JJ proteins_NN2 --_NN1 including_II fibronectin_NN1 ,_, the_AT laminins_NN2 and_CC collagens_NN2 and_CC others_NN2 --_NN1 that_CST provide_VV0 a_AT1 wide_JJ range_NN1 of_IO biochemical_JJ and_CC mechanical_JJ cues_NN2 to_II cells_NN2 ._. 
Studies_NN2 of_IO cellular_JJ processes_NN2 in_II the_AT laboratory_NN1 routinely_RR use_VV0 protein-coated_JJ dishes_NN2 to_TO mimic_VVI the_AT in_JJ21 vivo_JJ22 environment_NN1 and_CC to_TO elucidate_VVI the_AT functions_NN2 of_IO the_AT matrix_NN1 in_II regulating_VVG cellular_JJ processes_NN2 ._. 
The_AT adsorption_NN1 of_IO protein_NN1 ,_, however_RR ,_, is_VBZ complicated_JJ and_CC often_RR proceeds_VVZ with_IW a_AT1 lack_NN1 of_IO control_NN1 over_II the_AT orientation_NN1 and_CC conformation_NN1 of_IO proteins_NN2 at_II the_AT surface_NN1 ._. 
As_II a_AT1 result_NN1 ,_, it_PPH1 remains_VVZ difficult_JJ to_TO control_VVI the_AT biological_JJ activities_NN2 of_IO proteins_NN2 that_CST are_VBR adsorbed_VVN to_II man-made_JJ materials_NN2 ,_, and_CC in_II turn_NN1 compromises_NN2 the_AT use_NN1 of_IO these_DD2 substrates_NN2 as_CSA models_NN2 of_IO the_AT ECM_NP1 ._. 
This_DD1 realization_NN1 has_VHZ motivated_VVN a_AT1 significant_JJ effort_NN1 over_II the_AT past_JJ two_MC decades_NNT2 to_TO develop_VVI materials_NN2 that_CST present_JJ well-defined_JJ biological_JJ motifs_NN2 for_IF use_NN1 as_CSA mimics_NN2 of_IO the_AT ECM_NP1 ._. 
Many_DA2 of_IO the_AT approaches_NN2 have_VH0 used_VVN substrates_NN2 modified_VVN with_IW polymeric_JJ materials_NN2 or_CC monolayer_NN1 chemistries_NN2 that_CST can_VM be_VBI tailored_VVN with_IW cell_NN1 adhesion_NN1 motifs_NN2 ._. 
These_DD2 important_JJ approaches_NN2 have_VH0 been_VBN reviewed_VVN elsewhere_RL ._. 
The_AT present_JJ review_NN1 specifically_RR focuses_VVZ on_II the_AT use_NN1 of_IO self-assembled_JJ monolayers_NN2 of_IO alkanethiolates_NN2 on_II gold_NN1 for_IF this_DD1 application_NN1 ._. 
These_DD2 surfaces_NN2 are_VBR a_AT1 recent_JJ addition_NN1 to_II the_AT strategies_NN2 that_CST are_VBR now_RT used_VVN and_CC offer_VV0 a_AT1 set_NN1 of_IO characteristics_NN2 that_CST make_VV0 them_PPHO2 well-suited_JJ to_II certain_JJ classes_NN2 of_IO problems_NN2 in_II studies_NN2 of_IO cell-ECM_NP1 interactions_NN2 ._. 
These_DD2 characteristics_NN2 and_CC early_JJ applications_NN2 of_IO the_AT monolayers_NN2 are_VBR described_VVN in_II the_AT following_JJ pages_NN2 ._. 
Protein_NN1 adsorption_NN1 to_II materials_NN2 Most_RGT man-made_JJ materials_NN2 ,_, when_CS placed_VVN in_II solutions_NN2 containing_VVG proteins_NN2 ,_, are_VBR rapidly_RR coated_VVN with_IW an_AT1 adsorbed_JJ layer_NN1 of_IO protein_NN1 ._. 
This_DD1 property_NN1 is_VBZ exploited_VVN in_II the_AT routine_NN1 preparation_NN1 of_IO substrates_NN2 for_IF cell_NN1 culture_NN1 ._. 
For_REX21 example_REX22 ,_, polystyrene_NN1 substrates_NN2 are_VBR often_RR treated_VVN with_IW a_AT1 solution_NN1 of_IO fibronectin_NN1 prior_II21 to_II22 seeding_VVG with_IW cells_NN2 ._. 
The_AT resulting_JJ protein_NN1 film_NN1 is_VBZ heterogeneous_JJ in_II structure_NN1 --_NN1 in_CS21 that_CS22 the_AT proteins_NN2 are_VBR presented_VVN in_II a_AT1 range_NN1 of_IO orientations_NN2 and_CC denaturated_VVD states_NN2 --_JJ but_CCB still_RR presents_VVZ the_AT cell-binding_JJ motifs_NN2 at_II sufficient_JJ density_NN1 and_CC in_II a_AT1 functional_JJ conformation_NN1 to_TO promote_VVI attachment_NN1 ,_, spreading_VVG and_CC migration_NN1 ._. 
In_II practice_NN1 ,_, the_AT conditions_NN2 for_IF adsorbing_VVG protein_NN1 are_VBR identified_VVN empirically_RR and_CC depend_VV0 on_II the_AT structures_NN2 of_IO the_AT substrates_NN2 in_II ways_NN2 that_CST remain_VV0 poorly_RR understood_VVN ._. 
One_MC1 study_NN1 ,_, for_REX21 example_REX22 ,_, used_VVD atomic_JJ force_NN1 microscopy_NN1 and_CC surface_NN1 plasmon_NN1 resonance_NN1 spectroscopy_NN1 to_TO characterize_VVI fibrinogen_NN1 and_CC fibronectin_NN1 that_CST had_VHD adsorbed_VVN to_II monolayers_NN2 terminated_VVD either_RR in_II methyl_NN1 or_CC carboxyl_NN1 groups_NN2 and_CC found_VVD that_CST the_AT densities_NN2 and_CC conformations_NN2 of_IO the_AT adsorbed_JJ proteins_NN2 strongly_RR depended_VVN on_II surface_NN1 chemistry_NN1 ._. 
The_AT tendency_NN1 for_IF proteins_NN2 to_TO adsorb_VVI non-specifically_RR to_II materials_NN2 has_VHZ also_RR interfered_VVN with_IW efforts_NN2 to_TO use_VVI model_NN1 surfaces_NN2 that_CST present_NN1 defined_VVD cell-binding_JJ motifs_NN2 ._. 
When_CS the_AT slide_NN1 is_VBZ placed_VVN in_II a_AT1 suspension_NN1 of_IO cells_NN2 ,_, for_REX21 example_REX22 ,_, proteins_NN2 in_II the_AT medium_NN1 can_VM rapidly_RR adsorb_VVI to_II the_AT surface_NN1 ,_, thereby_RR physically_RR preventing_VVG access_NN1 to_II the_AT immobilized_JJ ligands_NN2 or_CC introduce_VV0 additional_JJ ligands_NN2 that_CST mediate_VV0 cell_NN1 attachment_NN1 ._. 
The_AT common_JJ approach_NN1 to_II this_DD1 problem_NN1 has_VHZ relied_VVN on_II treating_VVG the_AT substrate_NN1 with_IW a_AT1 solution_NN1 of_IO a_AT1 "_" blocking_JJ "_" protein_NN1 --_NN1 often_RR bovine_JJ serum_NN1 albumin_NN1 --_NN1 prior_II21 to_II22 cell_NN1 attachment_NN1 with_IW the_AT expectation_NN1 that_CST "_" sticky_JJ "_" sites_NN2 on_II the_AT surface_NN1 are_VBR passivated_VVN ,_, now_RT allowing_VVG the_AT ligands_NN2 to_TO mediate_VVI cell_NN1 adhesion_NN1 ._. 
But_CCB the_AT large_JJ fraction_NN1 of_IO the_AT surface_NN1 that_CST is_VBZ occupied_VVN by_II the_AT blocking_JJ protein_NN1 and_CC the_AT substantially_RR larger_JJR size_NN1 of_IO the_AT protein_NN1 relative_II21 to_II22 the_AT ligand_NN1 make_VV0 this_DD1 approach_NN1 ineffective_JJ in_II studies_NN2 that_CST require_VV0 molecular_JJ control_NN1 over_II the_AT surface_NN1 ._. 
Monolayers_NN2 for_IF cell_NN1 adhesion_NN1 This_DD1 same_DA approach_NN1 has_VHZ been_VBN validated_VVN for_IF studying_VVG the_AT roles_NN2 of_IO peptide_NN1 ligands_VVZ in_II cell_NN1 adhesion_NN1 and_CC migration_NN1 ._. 
In_II an_AT1 early_JJ example_NN1 ,_, we_PPIS2 had_VHD prepared_VVN monolayers_NN2 that_CST presented_VVD the_AT peptide_NN1 Gly-Arg-Gly-Asp-Ser_NP1 against_II a_AT1 background_NN1 of_IO tri_NN2 (_( ethylene_NN1 glycol_NN1 )_) groups_NN2 ._. 
This_DD1 peptide_NN1 is_VBZ found_VVN in_II fibronectin_NN1 and_CC other_JJ ECM_NP1 proteins_NN2 and_CC is_VBZ a_AT1 ligand_NN1 for_IF approximately_RR one-half_MF of_IO the_AT integrin_NN1 family_NN1 cell-surface_NN1 receptors_NN2 ,_, which_DDQ are_VBR an_AT1 important_JJ class_NN1 of_IO receptors_NN2 found_VVN on_II all_DB cellular_JJ surfaces_NN2 and_CC that_CST mediate_VV0 the_AT attachment_NN1 of_IO cells_NN2 to_II ECM_NP1 ._. 
We_PPIS2 found_VVD that_CST Swiss_JJ 3T3_FO fibroblasts_VVZ attached_JJ and_CC spread_VV0 efficiently_RR to_II the_AT monolayer_NN1 and_CC immunostaining_NN1 showed_VVD that_CST the_AT adherent_NN1 cells_NN2 assembled_VVD normal_JJ focal_JJ adhesion_NN1 complexes_NN2 --_NN1 a_AT1 cluster_NN1 of_IO integrin_NN1 receptors_NN2 that_CST forms_VVZ strong_JJ attachments_NN2 to_II the_AT substrate_NN1 and_CC initiates_VVZ adhesion_NN1 signals_VVZ --_JJ and_CC actin_NN1 stress_NN1 filaments_NN2 ._. 
Control_VV0 experiments_NN2 established_VVD that_CST the_AT adhesion_NN1 of_IO cells_NN2 could_VM be_VBI blocked_VVN with_IW a_AT1 soluble_JJ RGD_NP1 peptide_NN1 and_CC that_CST cells_NN2 failed_VVD to_TO attach_VVI to_II a_AT1 monolayer_NN1 presenting_VVG a_AT1 scrambled_JJ form_NN1 of_IO this_DD1 peptide_NN1 ._. 
Hence_RR ,_, this_DD1 work_NN1 validated_VVD the_AT use_NN1 of_IO monolayers_NN2 to_TO control_VVI the_AT ligand-receptor_JJ interactions_NN2 that_CST mediate_VV0 the_AT adhesion_NN1 of_IO cells_NN2 and_CC it_PPH1 also_RR showed_VVD that_CST the_AT ligand_NN1 RGD_NP1 alone_RR could_VM support_VVI cell_NN1 attachment_NN1 ,_, spreading_VVG and_CC a_AT1 proper_JJ organization_NN1 of_IO the_AT cytoskeleton_NN1 ._. 
Studies_NN2 of_IO cell-ECM_NP1 interactions_NN2 The_AT application_NN1 of_IO monolayer_NN1 substrates_NN2 to_II understanding_VVG the_AT roles_NN2 of_IO ligands_NN2 in_II fibronectin_NN1 illustrates_VVZ the_AT benefits_NN2 of_IO employing_VVG structurally_RR well-defined_JJ substrates_NN2 ._. 
Fibronectin_NN1 is_VBZ a_AT1 primary_JJ ECM_NP1 protein_NN1 that_CST is_VBZ found_VVN in_II many_DA2 tissues_NN2 ._. 
This_DD1 protein_NN1 comprises_VVZ more_DAR than_CSN 30_MC globular_JJ domains_NN2 that_CST include_VV0 the_AT type_NN1 III_MC domains_NN2 important_JJ for_IF cell_NN1 adhesion_NN1 ._. 
The_AT RGD_NP1 peptide_NN1 is_VBZ found_VVN within_II the_AT 10th_MD type_NN1 III_MC repeat_VV0 and_CC was_VBDZ among_II the_AT earliest_JJT ligands_NN2 discovered_VVD to_TO mediate_VVI cell_NN1 adhesion_NN1 by_II interacting_VVG with_IW integrin_NN1 receptors_NN2 ._. 
Recent_JJ work_NN1 has_VHZ implicated_VVN a_AT1 peptide_NN1 ,_, having_VHG sequence_NN1 PHSRN_NP1 ,_, residing_VVG in_II the_AT 9th_MD type_NN1 III_MC domain_NN1 in_II the_AT adhesion_NN1 of_IO cells_NN2 ._. 
A_AT1 series_NN of_IO studies_NN2 by_II Yamada_NP1 and_CC Grant_NP1 and_CC coworkers_NN2 led_VVN to_II the_AT proposal_NN1 that_CST PHSRN_NP1 is_VBZ a_AT1 synergy_NN1 peptide_NN1 that_CST cooperates_VVZ with_IW RGD_NP1 to_TO enhance_VVI the_AT attachment_NN1 and_CC spreading_NN1 of_IO cells_NN2 but_CCB that_DD1 fails_VVZ to_TO support_VVI cell_NN1 attachment_NN1 when_CS present_JJ alone_JJ ._. 
Mardon_NP1 suggested_VVD a_AT1 mechanism_NN1 wherein_RRQ the_AT RGD_NP1 and_CC PHSRN_NP1 peptides_NN2 in_II adjacent_JJ domains_NN2 of_IO fibronectin_NN1 simultaneously_RR interact_VV0 with_IW separate_JJ binding_JJ sites_NN2 on_II opposite_JJ sides_NN2 of_IO the_AT integrin_NN1 receptor_NN1 ._. 
This_DD1 model_NN1 was_VBDZ based_VVN on_II studies_NN2 of_IO cell_NN1 adhesion_NN1 to_II recombinant_JJ proteins_NN2 having_VHG scrambled_VVN RGD_NP1 and_CC PHSRN_NP1 sequences_NN2 and_CC on_II a_AT1 crystal_NN1 structure_NN1 of_IO a_AT1 fragment_NN1 of_IO fibronectin_NN1 ,_, which_DDQ shows_VVZ that_CST the_AT two_MC peptides_NN2 are_VBR directed_VVN towards_II the_AT same_DA region_NN1 of_IO space_NN1 and_CC are_VBR separated_VVN by_II a_AT1 distance_NN1 that_CST matches_VVZ the_AT width_NN1 of_IO the_AT receptor_NN1 ._. 
Yet_RR studies_VVZ that_CST use_VV0 protein-coated_JJ substrates_NN2 to_TO study_VVI cell_NN1 adhesion_NN1 are_VBR complicated_VVN by_II the_AT inability_NN1 to_TO establish_VVI that_DD1 peptide_NN1 sequences_NN2 in_II the_AT proteins_NN2 are_VBR available_JJ to_TO interact_VVI with_IW cellular_JJ receptors_NN2 once_RR the_AT proteins_NN2 are_VBR adsorbed_VVN to_II tissue_NN1 culture_NN1 plastic_NN1 ._. 
Monolayers_NN2 erase_VV0 this_DD1 ambiguity_NN1 and_CC were_VBDR used_VVN to_TO revise_VVI the_AT mechanistic_JJ understanding_NN1 of_IO the_AT synergy_NN1 peptide_NN1 ._. 
First_MD ,_, Baby_NN1 Hampster_NN1 Kidney_NN1 (_( BHK_NP1 )_) cells_NN2 attached_VVN with_IW similar_JJ efficiency_NN1 to_II monolayers_NN2 presenting_VVG either_RR the_AT RGD_NP1 or_CC the_AT PHSRN_NP1 peptide_NN1 ,_, although_CS cells_NN2 failed_VVD to_TO spread_VVI on_II the_AT latter_DA substrate_NN1 ._. 
Second_MD ,_, the_AT adhesion_NN1 of_IO cells_NN2 could_VM be_VBI inhibited_VVN by_II either_DD1 peptide_NN1 ,_, i.e._REX either_RR RGD_NP1 or_CC PHSRN_NP1 could_VM block_VVI the_AT attachment_NN1 of_IO cells_NN2 to_II a_AT1 monolayer_NN1 presenting_VVG RGD_NP1 (_( and_CC in_II the_AT same_DA sense_NN1 ,_, to_II a_AT1 monolayer_NN1 presenting_VVG PHSRN_NP1 )_) ._. 
These_DD2 results_NN2 require_VV0 that_CST the_AT two_MC peptides_NN2 either_RR share_VV0 a_AT1 binding_JJ site_NN1 on_II the_AT integrin_NN1 receptor_NN1 or_CC bind_VV0 to_TO separate_VVI sites_NN2 that_CST are_VBR allosterically_RR connected_VVN ._. 
In_II either_DD1 case_NN1 ,_, these_DD2 observations_NN2 are_VBR inconsistent_JJ with_IW the_AT standing_NN1 model_NN1 invoking_VVG a_AT1 cooperative_JJ two-point_JJ binding_NN1 of_IO peptides_NN2 ._. 
Indeed_RR ,_, the_AT ability_NN1 to_TO present_VVI defined_JJ ligands_NN2 at_II controlled_JJ densities_NN2 and_CC in_II a_AT1 regular_JJ environment_NN1 (_( to_TO ensure_VVI that_CST all_DB of_IO the_AT peptides_NN2 are_VBR active_JJ )_) against_II an_AT1 otherwise_RR non-interacting_JJ background_NN1 represents_VVZ a_AT1 powerful_JJ tool_NN1 for_IF establishing_VVG the_AT function_NN1 of_IO ECM_NP1 ligands_NN2 and_CC addressing_VVG the_AT relationship_NN1 between_II distinct_JJ ligands_NN2 ._. 
Dynamic_JJ substrates_NN2 The_AT self-assembled_JJ monolayers_NN2 have_VH0 enabled_VVN models_NN2 of_IO the_AT ECM_NP1 that_CST are_VBR dynamic_JJ ,_, and_CC that_CST allow_VV0 the_AT activities_NN2 of_IO immobilized_JJ ligands_NN2 to_TO be_VBI switched_VVN on_RP and_CC off_RP during_II the_AT course_NN1 of_IO cell_NN1 culture_NN1 ._. 
The_AT approach_NN1 exploits_NN2 the_AT conductivity_NN1 of_IO the_AT gold_NN1 film_NN1 that_CST supports_VVZ the_AT monolayer_NN1 and_CC follows_VVZ from_II extensive_JJ work_NN1 that_CST has_VHZ shown_VVN that_CST electroactive_JJ molecules_NN2 that_CST are_VBR tethered_VVN to_II the_AT monolayer_NN1 can_VM be_VBI reduced_VVN or_CC oxidized_VVD by_II applying_VVG electrical_JJ potentials_NN2 to_II the_AT gold_NN1 film_NN1 ._. 
By_II designing_VVG monolayers_NN2 that_CST incorporate_VV0 molecular_JJ groups_NN2 that_CST undergo_VV0 oxidation_NN1 or_CC reduction_NN1 and_CC subsequent_JJ reactions_NN2 ,_, it_PPH1 is_VBZ possible_JJ to_TO engineer_VVI surfaces_NN2 that_CST dynamically_RR inactivate_VV0 or_CC activate_VV0 ligands_NN2 that_CST interact_VV0 with_IW cell-surface_JJ receptors_NN2 ._. 
In_II one_MC1 example_NN1 ,_, the_AT RGD_NP1 peptide_NN1 was_VBDZ immobilized_VVN to_II a_AT1 monolayer_NN1 by_II31 way_II32 of_II33 a_AT1 tether_VV0 that_CST incorporated_VVD a_AT1 propanate-benzoquinone_JJ fragment_NN1 ._. 
The_AT peptide_NN1 ligand_NN1 mediated_VVD the_AT attachment_NN1 and_CC spreading_NN1 of_IO cells_NN2 and_CC was_VBDZ stable_JJ for_IF several_DA2 days_NNT2 ._. 
Application_NN1 of_IO a_AT1 negative_JJ potential_NN1 ,_, however_RR ,_, resulted_VVN in_II reduction_NN1 of_IO the_AT benzoquinone_NN1 group_NN1 and_CC subsequent_JJ lactonization_NN1 to_TO release_VVI the_AT peptide_NN1 from_II the_AT monolayer_NN1 ._. 
As_II a_AT1 result_NN1 ,_, the_AT adherent_NN1 cells_NN2 assumed_VVD a_AT1 rounded_JJ morphology_NN1 and_CC detached_VVN from_II the_AT substrate_NN1 ._. 
This_DD1 example_NN1 illustrates_VVZ the_AT molecular-level_JJ design_NN1 of_IO a_AT1 monolayer_NN1 that_CST could_VM selectively_RR release_VVI ligands_NN2 that_CST were_VBDR tethered_VVN by_II31 way_II32 of_II33 the_AT redox-active_JJ moiety_NN1 and_CC in_II this_DD1 case_NN1 non-invasively_RR release_VV0 an_AT1 adherent_NN1 cell_NN1 culture_NN1 ._. 
We_PPIS2 have_VH0 also_RR developed_VVN a_AT1 tether_VV0 that_CST released_VVD immobilized_JJ ligand_NN1 in_II31 response_II32 to_II33 a_AT1 positive_JJ electrical_JJ potential_NN1 ._. 
By_II combining_VVG these_DD2 two_MC strategies_NN2 with_IW microelectrode_NN1 arrays_NN2 ,_, it_PPH1 is_VBZ possible_JJ to_TO prepare_VVI adherent_NN1 cell_NN1 cultures_NN2 and_CC selectively_RR release_VV0 sub-populations_NN2 of_IO cells_NN2 at_II different_JJ times_NNT2 ._. 
Another_DD1 notable_JJ approach_NN1 to_II the_AT development_NN1 of_IO dynamic_JJ substrates_NN2 has_VHZ used_VVN polymeric_JJ gels_NN2 that_CST undergo_VV0 a_AT1 thermally_RR induced_VVN phase_NN1 transition_NN1 to_TO release_VVI cells_NN2 ._. 
The_AT approach_NN1 of_IO using_VVG physical_JJ organic_JJ chemistry_NN1 to_TO design_VVI molecules_NN2 or_CC polymers_NN2 that_CST undergo_VVI redox-active_JJ reactions_NN2 to_TO manipulate_VVI the_AT activities_NN2 of_IO ligands_NN2 on_II a_AT1 monolayer_NN1 is_VBZ general_JJ and_CC can_VM be_VBI applied_VVN to_II the_AT preparation_NN1 of_IO dynamic_JJ substrates_NN2 having_VHG a_AT1 range_NN1 of_IO activities_NN2 ._. 
In_II another_DD1 example_NN1 ,_, we_PPIS2 developed_VVD a_AT1 monolayer_NN1 that_CST could_VM be_VBI electrically_RR switched_VVN to_TO permit_VVI the_AT immobilization_NN1 of_IO cell-adhesive_JJ ligands_NN2 &rsqb;_) ._. 
A_AT1 monolayer_NN1 presenting_VVG the_AT hydroquinone_NN1 group_NN1 against_II a_AT1 background_NN1 of_IO tri_NN2 (_( ethylene_NN1 glycol_NN1 )_) groups_NN2 is_VBZ inert_JJ and_CC does_VDZ not_XX support_VVI the_AT attachment_NN1 of_IO cells_NN2 ._. 
Summary_NN1 and_CC outlook_NN1 This_DD1 review_NN1 provides_VVZ a_AT1 perspective_NN1 of_IO work_NN1 over_II the_AT past_JJ decade_NNT1 that_CST has_VHZ developed_VVN self-assembled_JJ monolayers_NN2 as_CSA model_NN1 substrates_NN2 for_IF studies_NN2 of_IO cell_NN1 adhesion_NN1 ._. 
Several_DA2 characteristics_NN2 inherent_JJ to_II the_AT monolayers_NN2 make_VV0 them_PPHO2 well-suited_JJ for_IF preparing_VVG mimics_NN2 of_IO the_AT ECM_NP1 ._. 
These_DD2 points_NN2 include_VV0 :_: Well-defined_JJ structure_NN1 ._. 
The_AT regular_JJ structure_NN1 of_IO the_AT monolayers_NN2 enables_VVZ wide_JJ flexibility_NN1 in_II tailoring_VVG the_AT surface_NN1 with_IW ligands_NN2 and_CC other_JJ functional_JJ groups_NN2 ._. 
Ligands_NN2 can_VM be_VBI presented_VVN with_IW excellent_JJ control_NN1 over_II their_APPGE densities_NN2 and_CC in_II a_AT1 uniform_JJ environment_NN1 ._. 
This_DD1 flexibility_NN1 also_RR enables_VVZ the_AT preparation_NN1 of_IO dynamic_JJ substrates_NN2 that_CST can_VM manipulate_VVI the_AT presentation_NN1 of_IO ligands_NN2 ._. 
Inert_JJ surfaces_NN2 ._. 
Self-assembled_JJ monolayers_NN2 that_CST present_JJ oligo_NN1 (_( ethylene_NN1 glycol_NN1 )_) groups_NN2 are_VBR highly_RR effective_JJ at_II preventing_VVG the_AT non-specific_JJ adsorption_NN1 of_IO protein_NN1 ._. 
These_DD2 surfaces_NN2 maintain_VV0 this_DD1 property_NN1 in_II complex_JJ solutions_NN2 ,_, including_II serum-containing_JJ cell_NN1 culture_NN1 media_NN and_CC void_VV0 the_AT need_NN1 for_IF blocking_VVG ._. 
Immobilization_NN1 schemes_NN2 ._. 
A_AT1 full_JJ portfolio_NN1 of_IO immobilization_NN1 chemistries_NN2 that_CST can_VM be_VBI used_VVN to_TO tether_VVI ligands_NN2 to_II monolayers_NN2 ,_, and_CC that_CST provide_VV0 for_IF a_AT1 defined_JJ orientation_NN1 of_IO the_AT ligands_NN2 and_CC a_AT1 rigorous_JJ control_NN1 over_II the_AT density_NN1 ,_, is_VBZ available_JJ ._. 
Analytical_JJ methods_NN2 ._. 
Monolayers_NN2 are_VBR compatible_JJ with_IW multiple_JJ analytical_JJ methods_NN2 used_VVN in_II characterizing_VVG biochips_NN2 ,_, including_II surface_NN1 plasmon_NN1 resonance_NN1 spectroscopy_NN1 ,_, fluorescence_NN1 imaging_NN1 ,_, radioisotope_VV0 detection_NN1 ,_, and_CC mass_JJ spectrometry_NN1 patterning_VVG methods_NN2 ._. 
The_AT availability_NN1 of_IO several_DA2 patterning_JJ methods_NN2 --_NN1 and_CC specifically_RR the_AT microcontact_NN1 printing_NN1 method_NN1 --_NN1 provides_VVZ routine_JJ access_NN1 to_II substrates_NN2 that_CST can_VM control_VVI the_AT shapes_NN2 ,_, sizes_NN2 and_CC positions_NN2 of_IO cells_NN2 ._. 
These_DD2 substrates_NN2 enable_VV0 studies_NN2 of_IO cytoskeleton_NN1 function_NN1 in_II cells_NN2 and_CC cell-based_JJ technologies_NN2 ._. 
Proven_JJ performance_NN1 ._. 
There_EX are_VBR hundreds_NNO2 of_IO publications_NN2 that_CST describe_VV0 the_AT use_NN1 of_IO monolayers_NN2 in_II biological_JJ and_CC bioanalytical_JJ applications_NN2 ._. 
These_DD2 systems_NN2 are_VBR well-suited_JJ to_II experiments_NN2 involving_VVG attached_JJ cell_NN1 cultures_NN2 and_CC are_VBR used_VVN commercially_RR in_II bioanalytical_JJ devices_NN2 ._. 
The_AT ECM_NP1 is_VBZ complex_JJ and_CC consequently_RR experimental_JJ studies_NN2 benefit_VV0 from_II a_AT1 range_NN1 of_IO methods_NN2 and_CC tools_NN2 that_CST bring_VV0 insights_NN2 to_II the_AT structures_NN2 and_CC functions_NN2 of_IO the_AT matrix_NN1 ._. 
The_AT self-assembled_JJ monolayers_NN2 represent_VV0 one_MC1 important_JJ component_NN1 of_IO this_DD1 toolbox_NN1 and_CC are_VBR significant_JJ because_CS they_PPHS2 offer_VV0 a_AT1 straightforward_JJ approach_NN1 to_TO prepare_VVI structurally_RR well-defined_JJ mimics_NN2 of_IO the_AT matrix_NN1 ._. 
The_AT tailored_JJ substrates_NN2 are_VBR admittedly_RR simple_JJ mimics_NN2 of_IO the_AT matrix_NN1 but_CCB they_PPHS2 allow_VV0 unambiguous_JJ studies_NN2 of_IO the_AT roles_NN2 that_CST discrete_JJ motifs_NN2 play_VV0 in_II mediating_VVG cell_NN1 adhesion_NN1 and_CC regulating_VVG downstream_RL signaling_VVG processes_NN2 ._. 
Early_RR work_VV0 with_IW the_AT monolayers_NN2 has_VHZ been_VBN important_JJ for_IF addressing_VVG the_AT roles_NN2 of_IO matrix_NN1 ligands_NN2 ,_, understanding_VVG the_AT relationships_NN2 between_II cell_NN1 shape_NN1 and_CC function_NN1 ,_, and_CC enabling_VVG a_AT1 class_NN1 of_IO dynamic_JJ substrates_NN2 that_CST can_VM modulate_VVI ,_, in_II real-time_NN1 ,_, the_AT activities_NN2 of_IO immobilized_JJ ligands_NN2 ._. 
Future_JJ work_NN1 will_VM see_VVI an_AT1 increased_JJ use_NN1 of_IO the_AT monolayers_NN2 for_IF current_JJ problems_NN2 in_II cell_NN1 adhesion_NN1 and_CC matrix_NN1 biology_NN1 ._. 
