Bundling and aggregation of DNA by cationic dendrimers

Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape. Among dendrimers, polyamidoamine (PAMAM) have received most attention as potential transfection agents for gene delivery, because these macromolecules bind DNA at physiological pH. The aim of this study was to examine the interaction of calf-thymus DNA with several dendrimers of different compositions, such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions, using constant DNA concentration and various dendrimer contents. FTIR, UV-visible, and CD spectroscopic methods, as well as atomic force microscopy (AFM), were used to analyze the macromolecule binding mode, the binding constant, and the effects of dendrimer complexation on DNA stability, aggregation, condensation, and conformation. Structural analysis showed a strong dendrimer-DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of K(mPEG-G3) = 1.5 (±0.5) × 10(3) M(-1), K(mPEG-G4) = 3.4 (±0.80) × 10(3) M(-1), and K(PAMAM-G4) = 8.2 (±0.90) × 10(4) M(-1). The order of stability of polymer-DNA complexation is PAMAM-G4 > mPEG-G4 > mPEG-G3. Both hydrophilic and hydrophobic interactions were observed for dendrimer-DNA complexes. DNA remained in the B-family structure, while biopolymer particle formation and condensation occurred at high dendrimer concentrations.     

Association of Influenza Virus Matrix Protein with Ribonucleoproteins

To characterize the sites and nature of binding of influenza A virus matrix protein (M1) to ribonucleoprotein (RNP), M1 of A/WSN/33 was altered by deletion or site-directed mutagenesis, expressed in vitro, and allowed to attach to RNP under a variety of conditions. Approximately 70% of the wild-type (Wt) M1 bound to RNP at pH 7.0, but less than 5% of M1 associated with RNP at pH 5.0. Increasing the concentration of NaCl reduced M1 binding, but even at a high salt concentration (0.6 M NaCl), approximately 20% of the input M1 was capable of binding to RNP. Mutations altering potential M1 RNA-binding regions (basic amino acids 101RKLKR105 and the zinc finger motif at amino acids 148 to 162) had varied effect: mutations of amino acids 101 to 105 reduced RNP binding compared to the Wt M1, but mutations of zinc finger motif did not. Treatment of RNP with RNase reduced M1 binding by approximately half, but even M1 mutants lacking RNA-binding regions had residual binding to RNase-treated RNP provided that the N-terminal 76 amino acids of M1 (containing two hydrophobic domains) were intact. Addition of detergent to the reaction mixture further reduced binding related to the N-terminal 76 amino acids and showed the greatest effect for mutations affecting the RNA-binding regions of basic amino acids. The data suggest that M1 interacts with both the RNA and protein components of RNP in assembly and disassembly of influenza A viruses.     

Computational and experimental analysis of drug binding to the Influenza M2 channel

The Influenza Matrix 2 (M2) protein is the target of Amantadine and Rimantadine which block its H⁺ channel activity. However, the potential of these aminoadamantyls to serve as anti-flu agents is marred by the rapid resistance that the virus develops against them. Herein, using a cell based assay that we developed, we identify two new aminoadamantyl derivatives that show increased activity against otherwise resistant M2 variants. In order to understand the distinguishing binding patterns of the different blockers, we computed the potential of mean force of the drug binding process. The results reveal that the new derivatives are less mobile and bind to a larger pocket in the channel. Finally, such analyses may prove useful in designing new, more effective M2 blockers as a means of curbing influenza. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.     

The interaction between severe acute respiratory syndrome coronavirus 3C-like proteinase and a dimeric inhibitor by capillary electrophoresis

3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been demonstrated to be a key target for drug design against SARS. The interaction between SARS coronavirus 3C-like (3CL) proteinase and an octapeptide interface inhibitor was studied by affinity capillary electrophoresis (ACE). The binding constants were estimated by the change of migration time of the analytes in the buffer solution containing different concentrations of SARS 3CL proteinase. The results showed that SARS 3CL proteinase was able to complex with the octapeptide competitively, with binding constants of 2.44 x 10(4) M(-1) at 20 degrees C and 2.11 x 10(4)M(-1) at 37 degrees C. In addition, the thermodynamic parameters deduced reveal that hydrophobic interaction might play major roles, along with electrostatic force, in the binding process. The ACE method used here could be developed to be an effective and simple way of applying large-scale drug screening and evaluation.     

Heparin binding to the urokinase kringle domain.

The binding of urokinase to immobilized heparin and dextran sulfate was studied using activity assays of the bound urokinase. The markedly higher binding observed with high M(r) urokinase compared to low M(r) urokinase indicated a role for the amino-terminal fragment (ATF). This was confirmed by the use of inactive truncated urokinase and monoclonal antibodies specific for the ATF in competition assays of urokinase binding. Antibody competition assays suggested a site in the kringle domain, and a synthetic decapeptide Arg-52-Trp-62 from the kringle sequence (kringle numbering convention) was competitive in assays of urokinase binding to dextran sulfate and heparin. Heparin binding to the urokinase kringle was unambiguously demonstrated via 1H NMR spectroscopy at 500 MHz. Effective equilibrium association constants (K(a)*) were determined for the interaction of isolated kringle fragment and low M(r) heparin at pH 7.2. The binding was strong in salt-free 2H2O (K(a)* approximately 57 mM-1) and remained significant in 0.15 M NaCl (K(a)* approximately 12 mM-1), supporting a potential physiological role for the interaction. This is the first demonstration of a function for the kringle domain of urokinase, and it suggests that while the classical kringle structure has specificity for lysine binding, there may also exist a class of kringles with affinity for polyanion binding.     

Catch bond-mediated adhesion without a shear threshold: trimannose versus monomannose interactions with the FimH adhesin of Escherichia coli

The FimH protein is the adhesive subunit of Escherichia coli type 1 fimbriae. It mediates shear-dependent bacterial binding to monomannose (1M)-coated surfaces manifested by the existence of a shear threshold for binding, below which bacteria do not adhere. The 1M-specific shear-dependent binding of FimH is consistent with so-called catch bond interactions, whose lifetime is increased by tensile force. We show here that the oligosaccharide-specific interaction of FimH with another of its ligands, trimannose (3M), lacks a shear threshold for binding, since the number of bacteria binding under static conditions is higher than under any flow. However, similar to 1M, the binding strength of surface-interacting bacteria is enhanced by shear. Bacteria transition from rolling into firm stationary surface adhesion as the shear increases. The shear-enhanced bacterial binding on 3M is mediated by catch bond properties of the 1M-binding subsite within the extended oligosaccharide-binding pocket of FimH, since structural mutations in the putative force-responsive region and in the binding site affect 1M- and 3M-specific binding in an identical manner. A shear-dependent conversion of the adhesion mode is also exhibited by P-fimbriated E. coli adhering to digalactose surfaces.     

Protein control of the redox potential of the primary quinone acceptor in reactioncCenters from Rhodobacter sphaeroides

The role of the protein environment in determining the redox midpoint potential (E(m)) of Q(A), the primary quinone of bacterial reaction centers, was investigated by mutation of isoleucine at position 265 of the M subunit in Rhodobacter sphaeroides. Isoleucine was changed to threonine, serine, and valine, yielding mutants M265IT, M265IS, and M265IV, respectively. All three mutants, with smaller residues replacing isoleucine, exhibited decreased binding affinities of the Q(A) site for various quinone analogues, consistent with an enlargement or loosening of the headgroup binding domain and a decrease in the van der Waals contact for small quinones. In all other respects, M265IV was like the wild type, but the polar mutants, M265IT and M265IS, had unexpectedly dramatic decreases in the redox midpoint potential of Q(A), resulting in faster rates of P(+)Q(A)(-) charge recombination. For both anthraquinone and native ubiquinone, the in situ E(m) of Q(A) was estimated to be approximately 100 and 85 mV lower in M265IT and M265IS, respectively. The effect on E(m)(Q(A)) indicates destabilization of the semiquinone or stabilization of the quinone. This is suggested to arise from either (i) electrostatic interaction between the partial charges or dipole of the residue hydroxyl group and the charge distribution of quinone and semiquinone states with particular influence near the C4 carbonyl group or (ii) from hydrogen bonding interactions between the hydroxyl oxygen and the N(delta)H of histidine M219, causing a weakening of the hydrogen bond to the C4 carbonyl. The rate of the first electron transfer (k(AB)(()(1)())) in the polar mutants was the same as in the wild type at low pH but decelerated at higher pH with altered pH dependence. The rate of the second electron transfer (k(AB)(()(2)())) was 3-4-fold greater than in the wild type over the whole pH range from 4 to 11, consistent with a larger driving force for electron transfer derived from the lower E(m) of Q(A).     

Influenza A Matrix Protein M1 Multimerizes upon Binding to Lipid Membranes

The matrix protein M1 plays a pivotal role in the budding of influenza virus from the plasma membrane (PM) of infected cells. This protein interacts with viral genetic material and envelope proteins while binding to the inner leaflet of the PM. Its oligomerization is therefore closely connected to the assembly of viral components and the formation of new virions. Of interest, the molecular details of M1 interaction with lipids and other viral proteins are far from being understood, and it remains to be determined whether the multimerization of M1 is affected by its binding to the PM and interaction with its components. To clarify the connection between M1 oligomerization and binding to lipid membranes, we applied a combination of several quantitative microscopy approaches. First, we used number and brightness (N&B) microscopy to characterize protein multimerization upon interaction with the PM of living cells. Second, we used controlled biophysical models of the PM (i.e., supported bilayers) to delve into the details of M1-lipid and M1-M1 interactions by employing a combination of raster image correlation spectroscopy (RICS), fluorescence correlation spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1 oligomer formation is strongly enhanced by membrane binding and does not necessarily require the presence of other viral proteins. Furthermore, we propose a specific model to explain M1 binding to the lipid bilayer and the formation of multimers.     

Influenza A Matrix Protein M1 Multimerizes upon Binding to Lipid Membranes

The matrix protein M1 plays a pivotal role in the budding of influenza virus from the plasma membrane (PM) of infected cells. This protein interacts with viral genetic material and envelope proteins while binding to the inner leaflet of the PM. Its oligomerization is therefore closely connected to the assembly of viral components and the formation of new virions. Of interest, the molecular details of M1 interaction with lipids and other viral proteins are far from being understood, and it remains to be determined whether the multimerization of M1 is affected by its binding to the PM and interaction with its components. To clarify the connection between M1 oligomerization and binding to lipid membranes, we applied a combination of several quantitative microscopy approaches. First, we used number and brightness (N&B) microscopy to characterize protein multimerization upon interaction with the PM of living cells. Second, we used controlled biophysical models of the PM (i.e., supported bilayers) to delve into the details of M1-lipid and M1-M1 interactions by employing a combination of raster image correlation spectroscopy (RICS), fluorescence correlation spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1 oligomer formation is strongly enhanced by membrane binding and does not necessarily require the presence of other viral proteins. Furthermore, we propose a specific model to explain M1 binding to the lipid bilayer and the formation of multimers.     

Exploring the binding mode of donepezil with calf thymus DNA using spectroscopic and molecular docking methods

Donepezil (DNP) is one of approved drugs to treat Alzheimer's disease (AD). However, the potential effect of DNP on DNA is still unclear. Therefore, the interaction of DNP with calf thymus DNA (DNA) was studied in vitro using spectroscopic and molecular docking methods. Steady‐state and transient fluorescence experiments showed that there was a clear binding interaction between DNP and DNA, resulting from DNP fluorescence being quenched using DNA. DNP and DNA have one binding site between them, and the binding constant (K_b) was 0.78 × 10⁴ L·mol^?1 at 298 K. In this binding process, hydrophobic force was the main interaction force, because enthalpy change (ΔH) and entropy change (ΔS) of DNP–DNA were 67.92 kJ·mol^?1 and 302.96 J·mol^?1·K^?1, respectively. DNP bound to DNA in a groove‐binding mode, which was verified using a competition displacement study and other typical spectroscopic methods. Fourier transform infrared (FTIR) spectrum results showed that DNP interacted with guanine (G) and cytosine (C) bases of DNA. The molecular docking results further supported the results of spectroscopic experiments, and suggested that both Pi‐Sigma force and Pi‐Alkyl force were the major hydrophobic force functioning between DNP and DNA.     

Electric-field dependent decays of two spectroscopically different M-states of photosensory rhodopsin II from Natronobacterium pharaonis

Sensory rhodopsin II (NpSRII) from Natronobacterium pharaonis was studied by resonance Raman (RR) spectroscopic techniques. Using gated 413-nm excitation, time-resolved RR measurements of the solubilized photoreceptor were carried out to probe the photocycle intermediates that are formed in the submillisecond time range. For the first time, two M-like intermediates were identified on the basis of their C=C stretching bands at 1568 and 1583 cm(-1), corresponding to the early M(L)(400) state with a lifetime of 30 micro s and the subsequent M(1)(400) state with a lifetime of 2 ms, respectively. The unusually high C=C stretching frequency of M(1)(400) has been attributed to an unprotonated retinal Schiff base in a largely hydrophobic environment, implying that the M(L)(400) --> M(1)(400) transition is associated with protein structural changes in the vicinity of the chromophore binding pocket. Time-resolved surface enhanced resonance Raman experiments of NpSRII electrostatically bound onto a rotating Ag electrode reveal that the photoreceptor runs through the photocycle also in the immobilized state. Surface enhanced resonance Raman spectra are very similar to the RR spectra of the solubilized protein, ruling out adsorption-induced structural changes in the retinal binding pocket. The photocycle kinetics, however, is sensitively affected by the electrode potential such that at 0.0 V (versus Ag/AgCl) the decay times of M(L)(400) and M(1)(400) are drastically slowed down. Upon decreasing the potential to -0.4 V, that corresponds to a decrease of the interfacial potential drop and thus of the electric field strength at the protein binding site, the photocycle kinetics becomes similar to that of NpSRII in solution. The electric-field dependence of the protein structural changes associated with the M-state transitions, which in the present spectroscopic work is revealed on a molecular level, appears to be related to the electric-field control of bacteriorhodopsin's photocycle, which has been shown to be of functional relevance.     

Deoxamuscaroneoxime derivatives as useful muscarinic agonists to explore the muscarinic subsite: demox, a modulator of orthosteric and allosteric sites at cardiac muscarinic M2 receptors

A series of muscarinic agonists, straight chained, branched, cyclic alkyl and aromatic derivatives of the oxime 1 (demox) was designed with the aim of investigating their activity on muscarinic receptor subtypes. Effects on M1 receptor were assessed functionally by a microphysiometer apparatus, while M2, M3, and M4 receptor potency and affinity were studied on isolated preparations of guinea pig heart, ileum, and lung, respectively. The results suggest that the substitution of a hydrogen with a long side-chain or bulky group generally induces a decrease in potency at M1 and M3 subtypes, while a general increase in this parameter is obtained at M2 subtype. Among the agonists 2-18, compound 4 behaves as a full agonist with a preference for M3 subtype. Moreover, compound 12 is inactive at M1 and M4 receptors while it displays a full agonist activity at M2 and M3 subtypes. Since demox displays a variable response on cardiac M2 receptors regulating heart force, an in-depth inquiry of the functional behaviour of this compound was carried out at M2 receptors. In presence of 10(-11) and 10(-10) M demox, the binding of [3H]-NMS was increased by approximately 30% as a consequence of an increase of the association of [3H]-NMS to membranes; this effect was not observed in presence of a higher concentration of [3H]-NMS. Higher concentrations of demox decreased the binding of [3H]-NMS to heart atrial membranes but significantly retarded the dissociation of this radioligand. Our results suggest that demox may interact with orthosteric and allosteric sites of atrial M2 muscarinic receptor.     

Activity-induced recovery of excitability in K(+)-depressed rat soleus muscle

Increased extracellular K(+) concentration ([K(+)](o)) can reduce excitability and force in skeletal muscle. Here we examine the effects of muscle activation on compound muscle action potentials (M waves), resting membrane potential, and contractility in isolated rat soleus muscles. In muscles incubated for 60 min at 10 mM K(+), tetanic force and M wave area decreased to 23 and 24%, respectively, of the control value. Subsequently, short (1.5 s) tetanic stimulations given at 1-min intervals induced recovery of force and M wave area to 81 and 90% of control levels, respectively, within 15 min (P < 0.001). The recovery of force and M wave was associated with a partial repolarization of the muscle fibers. Experiments with tubocurarine suggest that the force recovery was related to activation of muscle Na(+)-K(+) pumps caused by the release of some compound from sensory nerves in response to muscle activity. In conclusion, activity produces marked recovery of excitability in K(+)-depressed muscle, and this may protect muscles against fatigue caused by increased [K(+)](o) during exercise.     

Adsorption of the cationic antitumoral drug celiptium to phosphatidylglycerol in membrane model systems. Effect on membrane electrical properties

The binding of the cationic antitumoral drug Celiptium to the anionic phospholipid phosphatidylglycerol was studied by measuring surface potentials and surface pressures in monolayers, and by determination of electrophoretic mobility on liposomes. Surface potential and zeta potential data were interpreted in terms of the Gouy-Chapman-Stern theory of the diffuse electrical double layer. A unique drug-to-lipid adsorption constant KaD, could not be calculated. KaD was observed to increase rapidly from 10(4) M-1 to 10(6) M-1 with an increase in drug concentration from 5 x 10(-7) M to 7 x 10(-6) M. This was accompanied by a marked decrease (in absolute value) in the corresponding electrophoretic mobilities which, from negative at low drug concentrations, became positive at drug concentrations of 10(-5) M and above. This indicates that the drug-to-lipid binding cannot be accounted for by a simple Langmuir adsorption isotherm, but corresponds to a more complex process, probably of a cooperative nature. Comparison of delta V and zeta potential data shows that adsorption of Celiptium to phosphatidylglycerol not only lowers the electrical surface potential, psi 0 (in absolute value) but also markedly reduces the polarization potential, delta Vp. These observations suggest that Celiptium destabilizes the electrical properties of cell plasma membranes.     

Contrasting roles for domain 4 of VCAM-1 in the regulation of cell adhesion and soluble VCAM-1 binding to integrin alpha4beta1

Cell adhesion mediated by the interaction between integrin alpha4beta1 and VCAM-1 is important in normal physiologic processes and in inflammatory and autoimmune disease. Numerous studies have mapped the alpha4beta1 binding sites in VCAM-1 that mediate cell adhesion; however, little is known about the regions in VCAM-1 important for regulating soluble binding. In the present study, we demonstrate that 6D VCAM-1 (an alternatively spliced isoform of VCAM-1 lacking Ig-like domain 4) binds alpha4beta1 with a higher relative affinity than does the full-length form of VCAM-1 containing 7 Ig-like extracellular domains (7D VCAM-1). In indirect binding assays, the EC50 of soluble 6D VCAM-1 binding to alpha4beta1 on Jurkat cells (in 1 mM MnCl2) was 2 x 10(-9) M, compared with 7D VCAM-1 at 11 x 10(-9) M. When used in solution to inhibit alpha4beta1 mediated cell adhesion, the IC50 of 6D VCAM-1 was 13 x 10(-9) M, compared with 7D VCAM-1 measured at 150 x 10(-9) M. Removal of Ig-like domains 4, 5, or 6, or simply substituting Asp328 in domain 4 of 7D VCAM-1 with alanine, caused increased binding of soluble 7D VCAM-1 to alpha4beta1. In contrast, cells adhered more avidly to 7D VCAM-1 under shear force, as it induced cell spreading at lower concentrations than did 6D VCAM-1. Finally, soluble 6D VCAM-1 acts as an agonist through alpha4beta1 by augmenting cell migration and inducing cell aggregation. These results indicate that the domain 4 of VCAM-1 plays a contrasting role when VCAM-1 is presented in solution or as a cell surface-expressed adhesive substrate.     

Calcium binding to mixed cardiolipin-phosphatidylcholine bilayers as studied by deuterium nuclear magnetic resonance

Calcium binding to bilayer membranes containing cardiolipin (CDL) mixed with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was investigated by using phosphorus-31 and deuterium nuclear magnetic resonance (NMR) spectroscopy. The destabilizing effect of Ca2+ on CDL bilayers, including the formation of hexagonal H11 and isotropic phases, was eliminated when CDL was mixed with sufficiently large proportion of POPC. Thus, for the mixture CDL-POPC (1:9 M/M), 31P NMR spectra retained a line shape typical of fluid bilayer lipids even in the presence of 1.0 M Ca2+. Specifically head-group-deuteriated CDL or POPC showed in this mixture 2H NMR spectra indicating that both lipids remained in a fluidlike bilayer at Ca2+ concentrations up to 1.0 M. Any phase separation of Ca2-CDL clusters could be excluded. The residence time of Ca2+ at an individual head group binding site was shorter than 10(-6) s. The deuterium quadrupole splitting, delta nu Q, of POPC deuteriated at the alpha-methylene segment of the choline head group was found to be linearly related to the number of bound calcium ions, X2, for the CDL-POPC (1:9 M/M) mixture. The effective surface charge density, sigma, could be determined from the measured amount of bound Ca2+. Subsequently, the surface potential, psi 0, and the concentration of free Ca2+ ions at the plane of ion binding were calculated by employing the Gouy-Chapman theory. Various possible models of the equilibrium binding of Ca2+ could then be tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase

Isothermal titration calorimetry (ITC) was used to determine the thermodynamic driving force for inhibitor binding to the enzyme dihydrofolate reductase (DHFR) from Escherichia coli. 1,4-Bis-{[N-(1-imino-1-guanidino-methyl)]sulfanylmethyl}-3,6-dimethyl-benzene (1) binds DHFR:NADPH with a K(d) of 13±5 nM while the related inhibitor 1-{[N-(1-imino-guanidino-methyl)]sulfanylmethyl}-3-trifluoromethyl-benzene (2) binds DHFR:NADPH with a K(d) of 3.2±2.2 μM. The binding of these inhibitors has both a favorable entropy and enthalpy of binding. Additionally, we observe positive binding cooperativity between both 1 and 2 and the cofactor NADPH. Binding of compound 1 to DHFR is 285-fold tighter in the presence of the NADPH cofactor than in its absence. We did not detect binding of 2 to DHFR in the absence of NADPH. The backbone amide (1)H and (15)N NMR resonances of DHFR:NADPH and both DHFR:NADPH inhibitor complexes were assigned in order to better understand the binding of these inhibitors in solution. The chemical shift perturbations observed with the binding of 1 were greatest at residues closest to the binding site, but significant perturbations also occur away from the inhibitor location at amino acids in the vicinity of residue 58 and in the GH loop. The pattern of chemical shift changes observed with the binding of 2 is similar to that seen with 1. The main differences in chemical shift perturbation between the two inhibitors are in the Met20 loop and in residues at the interface between the inhibitor and NADPH.     

Studies of phenytoin binding to human serum albumin by high-performance affinity chromatography

High-performance affinity chromatography was used to study the binding of phenytoin to an immobilized human serum albumin (HSA) column. This was accomplished through frontal analysis and competitive binding zonal elution experiments, the latter of which used four probe compounds for the major and minor binding sites of HSA injected into the presence of mobile phases containing known concentrations of phenytoin. It was found that phenytoin can interact with HSA at the warfarin-azapropazone, indole-benzodiazepine, tamoxifen, and digitoxin sites of this protein. The association constants for phenytoin at the indole-benzodiazepine and digitoxin sites were determined to be 1.04 (+/-0.05) x 10(4)M(-1) and 6.5 (+/-0.6) x 10(3)M(-1), respectively, at pH 7.4 and 37 degrees C. Both allosteric interactions and direct binding for phenytoin appear to take place at the warfarin-azapropazone and tamoxifen sites. This rather complex binding system indicates the importance of identifying the binding regions on HSA for specific drugs as a means for understanding the transport of such substances in blood and in characterizing their potential for drug-drug interactions.     

Effects of Transcranial Direct Current Stimulation on the Control of Finger Force during Dexterous Manipulation in Healthy Older Adults

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.